NN0023

Research

on Heroin
Research

on Heroin

NN0023
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Introduction

The National Institute on Drug Abuse (NIDA) supports most of the world’s research on drug abuse and addiction.

NIDA-funded research enables scientists to apply the most advanced techniques available to the study of every aspect of

drug abuse, including:

• genetic and social determinants of vulnerability and response to drugs;

• short- and long-term effects of drugs on the brain, including addiction;

• other health and social impacts of drug abuse, including infectious diseases and economic costs;

• development and testing of medication and behavioral treatments for abuse and addiction; and

• development and evaluation of effective messages to deter young people, in particular, from abusing drugs.

Included in this document are selections of topic-specific articles reprinted from NIDA’s research newsletter, 

NIDA Notes. Six times per year, NIDA Notes reports on important highlights from NIDA-sponsored research, 

in a format that specialists and lay readers alike can read and put to use. Selections like the current one are intended 

to remind regular NIDA Notes readers and inform other readers of important research discoveries during the periods 

they cover.

We hope the information contained here answers your needs and interests. To subscribe to NIDA Notes and for further

information on NIDA’s drug abuse and addiction research, please visit our Web site at www.drugabuse.gov.
iii

Table of Contents

Interim Methadone Raises Odds of 

Enrolling in Comprehensive Treatment 

(V21-3; April 2007) . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Depot Naltrexone Appears Safe and Effective 

for Heroin Addiction (V21-3; April 2007) . . . . . . . . . . 3

Buprenorphine Plus Behavioral Therapy 

Is Effective For Adolescents With Opioid 

Addiction (V21-1; October 2006) . . . . . . . . . . . . . . . . 5

Study Finds Withdrawal No Easier With Ultrarapid

Opiate Detox (V21-1; October 2006) . . . . . . . . . . . . . 7

Network Therapy Enhances Office-Based 

Buprenorphine Treatment Outcomes

(V20-2; August 2005) . . . . . . . . . . . . . . . . . . . . . . . . . 9

Institute of Medicine Report Recommends NIDA

Research Agenda for New Addiction Therapies 

(V20-1; August 2005) . . . . . . . . . . . . . . . . . . . . . . . . 11

Once-A-Month Medication for Heroin Addiction?

(V19-3; September 2004) . . . . . . . . . . . . . . . . . . . . . . 13

Successful Trial Caps 25-Year Buprenorphine

Development Effort (V19-3; September 2004) . . . . . 14

Researchers Adapt HIV Risk Prevention Program

for African-American Women (V19-1; April 2004) . . 17

New Approaches Seek To Expand Naltrexone

Use in Heroin Treatment (V17-6; March 2003) . . . . . 20

Opening the Door to Mainstream Medical Treatment

of Drug Addiction (V17-5; January 2003) . . . . . . . . . 23

Buprenorphine Approval Expands Options for

Addiction Treatment (V17-4; November 2002) . . . . . 25

Combining Medications May Be Effective Treatment

for “Speedball” Abuse (V17-3; October 2002) . . . . . . 27

High-Risk Sex Is Main Factor in HIV Infection

for Men and Women Who Inject Drugs

(V17-2; May 2002) . . . . . . . . . . . . . . . . . . . . . . . . . . 29

Buprenorphine Taken Three Times per Week Is as

Effective as Daily Doses in Treating Heroin Addiction

(V16-4; October 2001) . . . . . . . . . . . . . . . . . . . . . . . . 31

33-Year Study Finds Lifelong, Lethal Consequences 

of Heroin Addiction (V16-4; October 2001) . . . . . . . 33

Buprenorphine Proves Effective, Expands 

Options For Treatment of Heroin Addiction 

(V16-2; May 2001) . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

Nicotine Craving and Heavy Smoking May 

Contribute to Increased Use of Cocaine and Heroin

(V15-5; October 2000) . . . . . . . . . . . . . . . . . . . . . . . . 36

Drug Abuse Treatment Programs Make Gains in

Methadone Treatment and HIV Prevention 

(V15-3; August 2000) . . . . . . . . . . . . . . . . . . . . . . . . 38

Recovery Harder for Addicts Who Start Young 

(V14-6; March 2000) . . . . . . . . . . . . . . . . . . . . . . . . . 40

High-Dose Methadone Improves Treatment 

Outcomes (V14-5; December 1999). . . . . . . . . . . . . . 41

Heroin Snorters Risk Transition To Injection 

Drug Use And Infectious Disease 

(V14-2; August 1999) . . . . . . . . . . . . . . . . . . . . . . . . . 43

Linking Medical Care With Drug Abuse 

Treatment Stems Tuberculosis Among 

HIV-Infected Drug Users (V13-3; July 1998) . . . . . . . 45
Interim Methadone Raises Odds of Enrolling in Comprehensive

Treatment

Patients reduced heroin abuse and criminal activity while awaiting admission to a treatment program.

By Sarah Teagle, NIDA NOTES Contributing Writer

Research Findings

Volume 21, Number 3 (April 2007)

Providing methadone maintenance to heroin addicts while

they are wait-listed for a treatment program can increase

the likelihood they will enroll when spaces open up, say

NIDA-funded researchers. The finding corroborates several previous studies in Europe and the United States. In the

new study, participants who received methadone maintenace reported reduced use and criminal activity.

Across the Nation, full-to-capacity opioid treatment programs commonly put heroin-addicted men and women

who present for treatment on waiting lists. By the time a

treatment slot becomes available, the deferred applicants

often have lost touch with the program or no longer 

desire treatment. The underlying idea of interim

methadone maintenance is to capitalize on individuals’

possibly transient motivation by providing help when help

is requested, explains Dr. Robert Schwartz, who conducted the study with colleagues from the Friends Research

Institute, the University of Maryland, and The Johns

Hopkins University.

Benefits Early and Late

The researchers recruited 319 heroin-addicted men and

women who placed themselves on the wait list of a single

community-based program for methadone maintenance.

The men and women typified people on methadone wait

lists in the Baltimore area, in that most were AfricanAmerican and reported abusing heroin daily as well as

cocaine during the past month. The investigators 

randomly assigned each individual to receive free interim

methadone maintenance for up to 120 days—the 

maximum time programs can legally provide methadone

to an unenrolled individual—or to remain on a wait list.

Both groups received information on how to access the

waiting lists of the 11 other public methadone programs

in the area.

The investigators interviewed each participant at the 

start of the study; upon his entry into comprehensive

methadone treatment or, if he or she did not go into 

treatment, after 120 days; and 6 months after the second

interview. Participants reported their alcohol, heroin, and

cocaine abuse and provided urine samples at all three time

points; those in the interim treatment group also provided 

samples at weeks 6 and 7 post-entry.

1
The results showed that 76 percent of study participants

receiving interim methadone entered comprehensive care

within 4 months, compared with only 21 percent in the

control group. At the time of the last interview, 78 percent

of interim methadone patients had entered a full-service 

program, compared with 33 percent of controls. Of the

study participants who entered comprehensive treatment

programs, 80 percent of those who had received interim

methadone and 64 percent of controls were still attending

at their last interviews.

The men and women who received interim treatment

reported abusing heroin on a mean of 4 of the last 30 days

prior to the 4-month followup interview, compared with

26 days for wait-listed patients. At the end of 4 months,

the interim methadone group had a 57 percent rate of

heroin-positive urine samples, while the control group had

a 79 percent positive rate (see chart, page 10 of Vol. 21

No. 3). The substantial difference in opiate-positive drug

tests remained at the last interview, with a 48 percent positive rate among interim-treated patients, compared to a

72 percent positive rate among controls. Participants who

received interim methadone reported spending less money

on drugs and receiving less illegal income in the past

month compared with controls. On average, study participants reported spending $872 monthly on illegal drugs at

the beginning of the study. By the end, the methadonemaintained participants had reduced these expenditures

dramatically, to an average of $76, compared with $560

among the controls—a difference that was also maintained at the 6-month followup. “If we can corroborate

this self-report data from other sources, the money saved

from not spending on drugs would more than pay for the

interim medication,” Dr. Schwartz notes. “It costs about

$20 to $30 per week per person. That is cheap, especially

when you consider the cost of criminal activity foregone,

and the hospitalizations and incarcerations avoided.”

While more of the participants who received methadone

entered full-service treatment, they took longer to do so 

(a mean of 117 days) compared to those in the control

group (59 days). However, Dr. Schwartz says, “People in

the interim group knew they were going to get full service

at the clinic where they were receiving their interim medication at the end of the study. Those in the control group

who accessed treatment probably represent a highermotivated subgroup—they actively sought it out using 

the local program information we gave them.”

Dr. Thomas Hilton of NIDA’s Division of Epidemiology,

Services and Prevention Research says, “Dr. Schwartz and

his team have demonstrated that interim medication is 

a significant recruitment tool. This might even be an

appropriate way to start treatment for everyone needing

methadone maintenance. It exposes patients to some

degree of structure, helps them ease into a more intensive,

full-service program and accommodate their lifestyle to

the structure required in the full service program.” Interim

methadone also may be an important tool for retention,

says Dr. Hilton, because patients may be ready for the

medication before they’re ready for counseling. After a few

months on methadone alone, patients may be better able

to engage with a counselor, making the relationship more

productive. Six methadone programs in the Baltimore area

have taken their cue from the study’s findings and now

offer interim maintenance. “What the interim treatment

approach does is add patients to existing programs,” 

Dr. Schwartz explains. “It is not hard for the staff to do,

it’s less expensive, and it’s effective. We hope it becomes

more widespread.”

Sources

• Schwartz, R.P., et al. A randomized controlled trial of

interim methadone maintenance. Archives of General

Psychiatry 63(1):102-109, 2006.

• Schwartz, R.P., et al. A randomized controlled trial of

interim methadone maintenance: 10-month followup. Drug and Alcohol Dependence [June 19, 2006

Epub Ahead of Print]. 

2

Study Specifics

Participants assigned to interim methadone began

receiving the medication on their second day in the

study, after completing an initial one-on-one orientation and physical exam. Nursing staff administered a

dose of 20 mg, which increased by 5 mg per day with

a target of 80 mg. Participants could slow or stop the

dose schedule by seeing a nurse; they could exceed

the 80 mg target by meeting with the program’s

emergency counselor. The only other service provided

was emergency counseling, and three interim participants requested and received emergency counseling

during the 4 months of treatment. Patients who

failed to show up for three consecutive doses were

discharged from the interm methadone—a programwide rule that did not change for study participants.

The clinic staff did not contact individuals who

missed doses. 
Depot Naltrexone Appears Safe and Effective for Heroin Addiction

A long-lasting, injectable formula of naltrexone performed well in a pilot clinical trial.

By Sarah Teagle, NIDA NOTES Contributing Writer

Research Findings

Volume 21, Number 3 (April 2007)

In a NIDA-supported pilot study, a new formulation of

naltrexone that patients receive by injection once every 

30 days appeared safe and helped heroin-addicted outpatients persevere in treatment. Investigators observed a

dose-dependent relationship between the medication,

called depot naltrexone, and patient retention rates.

Naltrexone helps patients overcome urges to abuse opiates

by blocking the drugs’ euphoric effects. Some patients do

well with it, but the oral formulation, the only one available to date, has a drawback: It must be taken daily, and 

a patient whose craving becomes overwhelming can obtain

opiate euphoria simply by skipping a dose before resuming abuse.

“What’s exciting about this slow-release formula is that it

provides continuous protection for a month at a time,

freeing patients from having to decide to take or not take

the medication every day,” says Dr. Sandra Comer, lead

investigator of the study. “By increasing treatment retention, depot naltrexone may allow patients greater contact

with appropriate supportive counseling and ease their

transition to a life without heroin.” 

Dr. Comer and her collaborators recruited 60 heroinaddicted, predominantly male (77 percent) adults, aged 18

to 59 years, through advertising in local newspapers and

word of mouth in New York City and Philadelphia. To be

eligible, patients could not be addicted to any drugs other

than heroin, caffeine, or nicotine. After initial heroin

detoxification, the investigators randomly assigned participants to receive low-dose depot naltrexone, high-dose

depot naltrexone, or placebo at the beginning of weeks 

1 and 5. All participants received twice-weekly relapse 

prevention behavioral therapy.

After 8 weeks, 68 percent of the patients receiving 384 mg

of naltrexone remained in treatment, compared to 60 percent of those receiving 192 mg, and 39 percent of those

on placebo. The percentage of urine samples negative for

opioids was highest for the group receiving 384 mg of 

naltrexone (62 percent) and lowest for the placebo group

(25 percent). After receiving the medication, patients in

the naltrexone groups reported “needing heroin” significantly less than those taking placebo.

The study participants experienced no apparent serious

side effects. Despite previous reports associating high

doses of naltrexone with hepatotoxicity, only one patient

developed elevated liver enzymes, which the researchers

attributed to a new-onset hepatitis C infection rather than

the medication. Heroin overdose, another potential concern for patients on naltrexone, was not observed in the

study; several patients did abuse heroin while on naltrexone, but reported no pleasure from it.

Encouraged by their results, Dr. Comer and her colleagues

are beginning a 6-month trial with a larger number of

participants. “We want to make sure the depot formula

helps over a longer period of time,” she explains. “Having

more tools is really helpful for providers. Some people do

better on methadone, others on naltrexone. We’ll have

more success if we can offer both.”

Dr. Richard Hawks of NIDA’s Division of

Pharmacotherapies and Medical Consequences of Drug

Abuse, says pharmaceutical companies are developing 

even longer-acting versions of naltrexone—a 6-month 

3
sustained-release formula. “But a drug alone never works,”

he says. “To be effective, the medication must be combined with behavioral therapy. Many years of behavioral

therapy research shows that the longer someone is in treatment, the longer the time to relapse. Longer-acting, sustained-release medications help maximize this effect.”

Source

• Comer, Sandra D., et al. Injectable, sustained-release

naltrexone for the treatment of opioid dependence.

Archives of General Psychiatry 63(2):210-218, 2006.

4
Buprenorphine Plus Behavioral Therapy Is Effective For

Adolescents With Opioid Addiction

A new study looks at extending the role of buprenorphine for treatment of adolescents.

By Patrick Zickler, NIDA NOTES Contributing Writer

Research Findings

Volume 21, Number 1 (October 2006)

Adolescents addicted to opioids responded better to

buprenorphine than clonidine in a clinical trial in which

all patients also received behavioral therapy. In the NIDAsupported comparison trial at the University of Vermont,

adolescents who received buprenorphine attended more

scheduled counseling sessions than peers who received

clonidine and had higher rates of successful induction to 

a relapse prevention regimen of naltrexone. The study, 

led by Dr. Lisa Marsch, is the first published randomized

controlled study of treatments for adolescents addicted 

to opioids.

“Heroin abuse among American teens has doubled over

the past decade, and abuse of prescription opioids such as

OxyContin and Vicodin has increased even more,” says

Dr. Marsch. “In light of those figures, it’s important to

have a scientific basis for selecting treatments for opioiddependent teens. We know from previous research and

clinical experience that buprenorphine and, to a lesser

extent, clonidine are among the medications that have

been shown to be effective for treating opioid-addicted

adults, but we haven’t known how helpful they can be 

for adolescents.” 

Dr. Marsch and colleagues enrolled 36 opioid-addicted

adolescents, aged 13 to 18, in a 28-day outpatient treatment program. Half the participants (9 male, 9 female)

received buprenorphine in tablet form, the rest (5 male,

13 female) clonidine via transdermal patch; each patient

also was given a placebo resembling the other treatment.

Medication dosages varied depending on each participant’s

weight and the amount of drug he or she reported abusing

before beginning treatment; dosages of buprenorphine

were in the low to moderate range of those typically given

to opioid-addicted adults.

All participants also received behavioral therapy based on

the Community Reinforcement Approach: three 1-hour

sessions each week of counseling on methods to minimize

involvement in situations that might lead to drug-taking,

training to help recognize and control urges to abuse opioids, and encouragement to recruit family members as

allies for abstinence. Participants earned vouchers worth

$2.50 for the first opioid-negative urine sample, plus an

additional $1.25 for each subsequent one, and a $10

bonus for each set of three consecutive negative samples.

Continuous abstinence could earn participants $152.50 in

vouchers redeemable for rewards such as ski passes, CDs,

gym passes, and clothing.

Buprenorphine and clonidine both supported high rates of

abstinence. Among participants who completed treatment,

rates were 78 percent and 81 percent, respectively, confirmed by urine samples provided at the thrice-weekly sessions. However, nearly twice as many buprenorphine as

clonidine recipients completed the 4-week treatment (72

percent compared with 39 percent). “The high rate of

retention in the buprenorphine group is particularly noteworthy,” Dr. Marsch says, “because long-term success in

recovery is directly related to the amount of time patients

spend in treatment.” And, she adds, the willingness of

most patients who received buprenorphine to continue

treatment with naltrexone following completion of the 28-

day program is similarly encouraging. Sixty-one percent of

the buprenorphine group, but only 5 percent of those who

received clonidine accepted naltrexone.

5
“Dr. Marsch’s research is an important first step in 

systematically studying adolescents who are addicted to

opioids,” says Dr. Ivan Montoya of NIDA’s Division of

Pharmacotherapies and Medical Consequences of Drug

Abuse. “We know that there are differences in the patterns

of opiate abuse and addiction in young people compared

with adults. We need dedicated studies like this one to

understand how teens are affected by opiate drugs and

how best to treat them.”

The next step in Dr. Marsch’s research will involve a larger

sample of young opioid abusers. “We want to evaluate

buprenorphine’s effectiveness if treatment is extended to 

2 months rather than 28 days,” she says. “We will also

examine the most effective doses and dosing regimens for

various subgroups of young patients.”

Source

• Marsch, L.A., et al. Comparison of pharmacological

treatments for opioid-dependent adolescents: A randomized controlled trial. Archives of General Psychiatry

62(10):1157-1164, 2005. 

6
Study Finds Withdrawal No Easier With Ultrarapid Opiate Detox

Three serious adverse events among 35 ultrarapid procedures were all related to unreported preexisting

medical conditions.

By Lori Whitten, NIDA NOTES Staff Writer

Research Findings

Volume 21, Number 1 (October 2006)

Heroin-addicted patients who undergo so-called ultrarapid,

anesthesia-assisted detoxification suffer withdrawal symptoms as severe as those endured by patients in detoxification

by traditional methods, according to a NIDA-funded clinical trial. Researchers Dr. Eric Collins and colleagues at the

College of Physicians and Surgeons of Columbia University

concluded that there is no compelling reason to use general

anesthesia in the treatment of opiate dependence, especially

as it presents particular safety concerns. The new findings

corroborate those of three international studies.

The ultrarapid detox technique, developed about 15 years

ago by clinicians who hoped to mitigate the discomfort of

withdrawal and speed the initiation of relapse prevention

therapy, relies on a general anesthetic to sedate the patient

for several hours while an opiate blocker precipitates withdrawal. The method is not covered by insurance, which

makes it difficult to determine how many patients have

received anesthesia-assisted detox. 

To compare anesthesia-assisted detox with other approaches, Dr. Collins and colleagues enrolled 106 people seeking

heroin detox at Columbia University Medical Center’s

Clinical Research Center. The patients, aged 21 through 50,

had abused heroin every day during the past month. All

spent 3 days as Center inpatients during detox, then were

scheduled for twice-weekly outpatient relapse prevention

psychotherapy and naltrexone maintenance (50 mg/day) for

12 weeks.

The investigators randomly assigned the participants to 

one of three detox methods (see chart). The goal of each

method was to minimize patients’ discomfort during withdrawal. In the ultrarapid approach, physicians put patients

under anesthesia for 4 to 6 hours while administering 

naltrexone, a medication that precipitates withdrawal by

blocking opioid molecules from their receptors in the brain.

In the second method, patients remained awake and took 

a single dose of buprenorphine, a medication that eases

7
withdrawal symptoms by moderating and smoothing the

rate of opioid clearance from the brain. In the third

approach, patients also remained awake and received clonidine and other nonopioid medications as needed to counter

symptoms for all 3 inpatient days. These medications were

available to all groups as needed for the duration of the

inpatient phase. Throughout detox, the researchers closely

monitored patients for complications, assessed physical

indications of withdrawal, and asked the participants to rate

their subjective experiences.

Once awakened from anesthesia, patients in the ultrarapid

detox group demonstrated and reported symptoms of discomfort comparable to those experienced by participants

receiving the buprenorphine- and clonidine-assisted 

methods (see chart). Three patients receiving the anesthesiaassisted method experienced serious adverse events—pulmonary and psychiatric complications as well as a metabolic

complication of diabetes, all of which required hospitalization. The complications were related to preexisting medical

conditions that the patients had failed to reveal when they

were screened for admission into the study. No adverse

events occurred with the other detox methods.

Treatment outcomes among the three groups were similar.

Following detox, the researchers offered all the patients

relapse prevention therapy consisting of outpatient counseling and naltrexone, which counteracts the pleasurable

effects of subsequently administered opioids. More than 

90 percent of the patients who received the anesthesia- and

buprenorphine-assisted detox completed naltrexone induction; only 21 percent of those receiving clonidine completed induction. By the third week, more than half the

patients in all three groups had dropped out of the study;

only 18 percent remained in treatment the full 12 weeks.

The percentages of patients submitting opiate-positive urine

samples during outpatient treatment also were comparable,

roughly 63 percent, across the three detox methods. 

“No Advantage”

“Although providers advertise anesthesia-assisted detox as a

fast and painless method to kick opiate addiction, the evidence does not support those statements,” says Dr. Collins.

“Patients should consider the many risks associated with

this approach, including fluid accumulation in the lungs,

metabolic complications of diabetes, and a worsening of

underlying bipolar illness, as well as other potentially serious adverse events,” he says. Those with preexisting medical

conditions—including some psychiatric disorders, elevated

blood sugar, insulin-dependent diabetes, prior pneumonias,

hepatitis, heart disease, and AIDS—are particularly at risk

for anesthesia-related adverse events. “Careful screening is

essential with the anesthesia-assisted method, because the

thought of sleeping through withdrawal is so compelling

that some patients may conceal their medical histories,” says

Dr. Collins.

“We now have several rigorous studies indicating that anesthesia-assisted detox—a costly and risky approach—offers

no advantage over other methods,” says Dr. Ivan Montoya

of NIDA’s Division of Pharmacotherapies and Medical

Consequences of Drug Abuse. Dr. Montoya notes, “The

low retention of patients in subsequent outpatient treatment

in the present study, which is not unusual for the opiateaddicted population, highlights the need to engage people in

long-term recovery after detoxification.” Naltrexone can help

motivated patients stay off opiates, but many do not stick to

the regimen of daily tablets because of the medication’s side

effects of anxiety and restlessness. Long-acting monthly injections of naltrexone, which are now available for alcoholism

treatment, may work better for patients and show promise in

NIDA-supported clinical trials. 

Dr. Montoya also points out that with the current epidemic

of prescription painkiller abuse, clinicians need more

research on cost-effective detox methods for these opiates

(see “2003 Survey Reveals Increase in Prescription Drug

Abuse, Sharp Drop in Abuse of Hallucinogens” NIDA

Notes, Vol. 19, No. 4). Some clinics are using buprenorphine for this purpose, and NIDA-funded investigators are

studying various methods to improve prescription opiate

detox and help patients engage in longer term treatment.

Source

• Collins, E.D., et al. Anesthesia-assisted vs buprenorphine- or clonidine-assisted heroin detoxification and

naltrexone induction: A randomized trial. Journal of the

American Medical Association 294(8):903-913, 2005.

8
9

Network Therapy Enhances Office-Based Buprenorphine Treatment

Outcomes

By Lori Whitten, NIDA NOTES Staff Writer

Research Findings

Volume 20, Number 2 (August 2005)

Network therapy—an office-based behavioral treatment that engages family and

close friends in the recovery process—

enhances abstinence among outpatients

being treated with buprenorphine for opioid addiction. By the end of an 18-week

NIDA-funded study, abstinence rates of

patients who participated in network therapy (NT) were twice as high as those of a

comparison group receiving standard

medication management (MM) along

with buprenorphine.

“NT transforms a few close relations from

well-wishers to a team with skills to help

patients achieve and maintain abstinence,”

says Dr. Marc Galanter, lead investigator

of the study. In previous research, Dr.

Galanter and his colleagues showed NT’s

promise as a therapy for cocaine addiction

in both office- and community-based

treatment settings; the new results in

patients with opioid addiction add to the

hopes that NT may offer a psychosocial

adjunct to office-based buprenorphine

treatment.

Dr. Galanter and colleagues at New York University

Medical Center treated 66 heroin-addicted outpatients,

aged 21 to 65, who reported abusing the drug for 12 years

on average. Most (73 percent) had previous experience

with addiction treatment, and about a third (30 percent)

had tried methadone maintenance. Most lived with family

or friends (77 percent) and were employed (67 percent).

The investigators selected patients who could form a network—a few drug-free relatives or friends willing to help

the patient achieve and maintain abstinence—and randomly assigned them to either MM or NT. 

All patients received a standard course of combined

buprenorphine/naloxone tablets (16 mg/4 mg a day) taken

under the tongue. Each patient also participated in two

half-hour sessions per week of psychosocial treatment—

either NT or MM—with a resident training in psychiatry.

In MM, the therapist monitors the patient’s response to

the medication and encourages him or her to abstain from

opioid abuse. The number of MM sessions and time

investment are equivalent to those of NT, but the patient

does not learn specific behavioral strategies for maintaining abstinence.

At the beginning of the study, patients chose people with

whom they had an enduring relationship. Two people, on

average, participated in each NT session with the patient.

From the first NT session, therapists emphasized the primary guideline for this treatment approach: to focus on

helping the patient achieve abstinence and to avoid discussions of relationship history, blaming, and emotional conflict. During sessions once a week, patients and their

helpers communicated openly about events and people

related to the patient’s drug abuse and learned cognitivebehavioral techniques used widely in relapse prevention.

As the supporters developed an understanding of relapse 

prevention, they helped the patient anticipate problem situations and develop recovery plans. They concentrated on

creating an environment that helped the patient establish

a drug-free residence, avoid substance-abusing peers, and

stick to a medication regimen. 

Network Therapy Increases Abstinence Among 

Patients Taking Buprenorphine

Among patients taking buprenorphine for heroin addiction, more of those who participated in network therapy attained abstinence during the 18-week study and throughout

the last 3 weeks of treatment, compared with those who participated in medication

management.
Although network members offer active support, patients

in NT take full responsibility for their recovery. In weekly

one-on-one sessions with a therapist, patients in the study

strengthened the cognitive-behavioral skills they learned in

network sessions, including monitoring of drug-abuse triggers, coping with craving, managing stress, and problemsolving. Patients made and carried tools to assist them in

recovery, such as cards to help them weigh drugs’ attractions against the costs of abuse, written plans to deal with

emergencies, and contact information for network members. The therapist encouraged patients to participate in

12-step programs, which can offer role models for abstinence and friendships with nonabusers. Throughout treatment, the researchers verified abstinence from illicit opioids with weekly urine tests.

Patients participating in MM and NT spent the same

amount of time in therapy, 70 days on average, but more

NT participants achieved abstinence by the end of treatment. Half receiving NT attained this goal, confirmed by

opioid-free urine tests, during the last 3 weeks of treatment, compared with 23 percent of MM patients. More

NT than MM patients produced opioid-free urine samples during the study (65 percent versus 45 percent). NT

patients participated in 10 network sessions on average;

those who attended more sessions sustained abstinence

longer during the study. Whether the network comprised

family or friends did not affect treatment outcomes. 

An Office-Based Approach

“My colleagues and I designed NT principally for addiction treatment providers who do not have a large support

team,” Dr. Galanter says. “We find that those with psychotherapy experience learn the NT approach in about 

10 training sessions with subsequent supervision.” (See

“Network Therapy Expands Treatment Capabilities of

Small Practice Providers,” NIDA NOTES, Vol. 18, No. 2,

p. 5.) 

“In this approach, a patient and therapist collaborate with

a small group to achieve stable abstinence, weaving the

contributions of each member and different treatment

techniques into a supportive tapestry for a drug-free

lifestyle. The network counteracts the environmental and

social factors—for example, substance-abusing peers—that

often compromise recovery,” says Dr. Galanter. Although

NT can help patients who have a few close associates willing to support their recovery, the therapy is probably not

appropriate for homeless or mentally ill people or those

who cannot achieve abstinence on their own for even 1

day.

Studies show that many heroin-addicted patients in treatment continue to abuse some form of opioids, with only

about 20 percent of those on buprenorphine medication

demonstrating opioid-negative urine tests at the end of 1

month of treatment. Extending the therapy to 2 to 6

months increases the percentage of opioid-negative urine

tests to 50 to 60 percent. Dr. Dorynne Czechowicz of

NIDA’s Division of Clinical Neuroscience, Development

and Behavioral Treatment says, “It’s impressive that NT

therapy enhanced the results typically seen with shortterm buprenorphine medication.” She emphasizes that the

researchers should examine whether NT reduces abuse of

other drugs among opioid-addicted patients, particularly

cocaine, which puts people who are in recovery at high

risk for opioid abuse relapse. She adds that investigators 

should also conduct longer-term studies to determine

whether patients maintain these treatment gains and

demonstrate NT’s effectiveness in general medical practice. 

Dr. Galanter and his colleagues have posted a brief introduction to NT on the Internet (http://www.med.nyu.

edu/substanceabuse/manuals/nt/). The American Psychiatric

Association sells a training video on NT as an office-based

addiction treatment; the video is appropriate for any mental health professional (http://www.appi.org/book.cfm?id=

62142). 

Source

• Galanter, M., et al. Network therapy: Decreased 

secondary opioid use during buprenorphine maintenance. Journal of Substance Abuse Treatment

26(4):313-318, 2004. 

10

As the supporters developed an

understanding of relapse prevention,

they helped the patient anticipate

problem situations and develop 

recovery plans.

“The network counteracts 

the environmental and social 

factors—for example, 

substance-abusing peers—that 

often compromise recovery.”
Institute of Medicine Report Recommends NIDA Research Agenda

for New Addiction Therapies

By Patrick Zickler, NIDA NOTES Staff Writer

Research Findings

Volume 20, Number 1 (August 2005)

A mother asks a pediatrician to vaccinate her child against

nicotine’s pleasurable effects, practically eliminating the

possibility that the child will become a smoker. A patient

in treatment for heroin addiction receives an injection of

sustained-release medication that will prevent her from

feeling the drug’s euphoric effects for a year. As current

drug abuse research brings such scenarios closer to realization, NIDA has begun to study the broad implications of

these and other new types of preventive treatment. These

therapies underscore the need to balance therapeutic benefits and ethical considerations, particularly if the person

receiving treatment—a minor child or a person involved

in the criminal justice system, for example—is not the

person who chooses it. 

At NIDA’s request, the National Research Council’s

Institute of Medicine (IOM) identified ethical, legal, and

behavioral issues that must be considered in the development and application of active and passive immunotherapies and sustained-release medication. The Institute’s

306-page report recommends a set of guiding principles as

NIDA-supported research pursues the development of

these potentially powerful new preventive interventions.

Immunotherapies destroy drug molecules before they

reach the brain. Active immunotherapy involves a vaccine

that stimulates the body’s immune system to create antibodies against drugs in the same way that an inoculation

creates antibodies against polio or measles virus. Passive

immunotherapy involves periodic injections of antibodies

rather than stimulation of the immune system; an example of this type of therapy is tetanus immune globulin,

which contains antibodies to provide short-term protection for someone whose injury may have exposed them to

soil-borne tetanus bacteria. Sustained-release therapies

involve injection or implantation of long-acting formulations of medications that are released over a period of

weeks or months to block the effect of drugs in the brain. 

The IOM report identifies ways to meet the challenges

these interventions are likely to pose for researchers, treatment providers, policymakers, parents, and the public.

Because the treatments may have lifelong effects, IOM

recommends long-term studies involving animals of different ages, as well as their offspring, before human studies

are undertaken.

IOM also recommends studies that can be used to 

establish clear guidelines for use of the new therapies in

circumstances that are inherently coercive or nonconsensual, such as in the criminal justice system, child welfare

cases, or the protective immunization of minor children.

What, for example, are the possible legal consequences of

administering immunotherapy medications to children or 

adolescents? Competent adults have the right to decline

medical treatment, but the legal situation is more complicated when the patient is a minor and decisions made by

others on his or her behalf may have a lifelong effect.

Immunotherapies will leave long-lasting biological traces

that can be detected in routine blood or urine tests. Such

markers could label patients as drug abusers long after

they have entered sustained recovery, which could discourage some from utilizing these treatments. In its report,

11
IOM says the development of immunotherapy and sustained-release medications highlights the need to understand addiction as a chronic medical condition that

requires long-term management, a partnership between

primary medical care and addiction treatment, and 

integration of psychosocial services into the treatment

environment. The IOM report recommends that NIDA

support models that integrate the new pharmacotherapies

with psychosocial services in addiction treatment and primary care settings that reduce the stigma of substance

abuse treatment. 

The full report, New Treatments for Addiction: Behavioral,

Ethical, Legal, and Social Questions, is available online at

www.nap.edu/catalog/10876.html. 

12
Once-A-Month Medication for Heroin Addiction?

By Kimberly R. Martin, NIDA NOTES Contributing Writer 

Research Findings

Volume 19, Number 3 (September 2004)

A single injection of a new sustainedrelease formulation of buprenorphine substantially blocked heroin’s effects and

relieved heroin craving and withdrawal

symptoms for up to 6 weeks, report

researchers at the Behavioral Pharmacology Research Unit at The Johns

Hopkins University School of Medicine

in Baltimore.

The study, the first to test sustainedrelease buprenorphine in human opioid

addicts, affirms the promise of a formulation designed to increase patient adherence to treatment, ease the burden

of visits to treatment providers, and

reduce the risk of buprenorphine misuse.

Dr. George Bigelow and colleagues evaluated the formulation with five patients,

two men and three women aged 33 to 42,

who had been using heroin more than 6

years on average and were current daily

users. The day before initiating buprenorphine, the researchers administered oral doses of hydromorphone as clinically needed to suppress the patients’

withdrawal symptoms. The amount of hydromorphone

needed to alleviate withdrawal symptoms is an objective

measure of opioid dependence severity. The patients’ average opioid addiction was approximately equivalent to 50

mg/day of methadone. Buprenorphine treatment consisted

of a single injection of biodegradable polymer microcapsules containing 58 mg of the medication. During the following 6 weeks—a 4-week residential phase and a 2-week

outpatient phase—researchers assessed the patients for

signs of heroin withdrawal and patients rated their withdrawal symptoms using a standard questionnaire. No

patient needed additional medication for withdrawal

relief.

To test sustained-release buprenorphine’s power to block

the effects of heroin-like opioids, patients received weekly

challenge test injections of 3 mg hydromorphone or saline

under double-blind procedures. Patients’ subjective ratings

of various hydromorphone effects—such as feeling high,

sick, or any effect—stood at zero in the first 2 weeks after

buprenorphine treatment. Drug effect ratings in subsequent weeks of the study remained low—less than 25 on

a 100-point scale. Moreover, the buprenorphine formulation appeared to be safe and well tolerated, with no significant side effects or signs of opioid intoxication or respiratory depression. These results suggest that sustainedrelease buprenorphine may prove an appealing and effective treatment option for opioid-addicted patients and

their physicians.

Source

• Sobel, B.F.; Sigmon, S.C.; Walsh, S.L.; Johnson, R.E.;

Liebson, I.A.; Nuwayser, E.S.; Kerrigan, J.H.; and

Bigelow, G.E. Open-label trial of an injection depot

formulation of buprenorphine in opioid detoxification. Drug and Alcohol Dependence 73(1):11-22, 2004.

13

Mean Withdrawal Ratings

Withdrawal Suppression

Self-Report Ratings

0

5

10

15

20

25

Pre-Injection

Day

Week

1

Week

2

Week

3

Week

4

Injection

Day

Long-Lasting Buprenorphine Reduces Withdrawal

Symptoms in Heroin-Dependent Patients

A new long-lasting, sustained-release form of buprenorphine given by a single injection

reduced patients’ heroin withdrawal symptoms for 4 weeks after treatment.
Successful Trial Caps 25-Year Buprenorphine Development Effort

By Arnold Mann, NIDA NOTES Contributing Writer

Research Findings

Volume 19, Number 3 (September 2004)

Twenty-five years ago it would have been almost impossible to imagine a treatment for opiate addiction that could

be prescribed in a physician’s office, picked up at a pharmacy, and taken at home. But that scenario has been

achieved after a quarter-century of collaborative effort—

and the overcoming of several barriers—by NIDA’s medication development program and Reckitt Benckiser

Pharmaceuticals, Inc.

Dr. Don Jasinski, a scientist at NIDA’s Intramural

Research Program (IRP), was the first to recognize the

characteristics of buprenorphine—developed in the 1970s

as an injectable pain medication—as useful for addiction

treatment. He led the initial 1978 study demonstrating

the drug’s effectiveness and its acceptability to patients as a

treatment for opiate dependence.

Early on, NIDA scientists realized that medications for

addiction not only had to be safe and efficacious, but also

had to be available in a form that would be practical for

therapeutic use over the long term. NIDA worked with

Reckitt Benckiser (then Reckitt & Colman) to develop

noninjectable formulations of buprenorphine; by 1990,

Dr. Ed Johnson and colleagues at the IRP demonstrated

that a solution form of the drug administered under the

tongue was safe, effective, and acceptable to patients as an

opiate dependence treatment.

As with any opioid, however, there were concerns about

buprenorphine diversion and the potential for abuse.

NIDA again collaborated with the manufacturer, and by

the mid-1990s, developed a combination tablet of

buprenorphine and naloxone that would minimize the

potential for abuse—a development that put the vision of

take-home treatment for opiate dependence within reach.

In the next decade, scientists at NIDA and Reckitt

Benckiser conducted clinical trials with more than 2,400

patients that established buprenorphine’s safety and efficacy in treating opiate dependence. And finally, a NIDAfunded collaborative clinical trial, codirected by Dr. Paul

Fudala of the Veterans Affairs Medical Center and the

University of Pennsylvania in Philadelphia, established the

safety and effectiveness of the buprenorphine-naloxone

combination as a prescribed take-home treatment. Data

from this study and two other pivotal trials formed the

basis for the U.S. Food and Drug Administration’s (FDAs)

approval of buprenorphine and the combination medication in 2002.

“People at NIDA knew of the great need to move opiate

addiction treatment from the traditional clinic settings to

individual physicians’ offices. But we had to address concerns about diversion and unprescribed use. Drs. Jasinski,

Johnson, and Fudala deserve a great deal of credit for their

contributions to this collaborative achievement—a safe

and effective take-home treatment with minimal likelihood for abuse,” says Dr. Frank Vocci, director of NIDA’s

Division of Treatment Research and Development.

Dr. Fudala’s research, a nationwide study of 472 opiateaddicted men and women, was codirected by Dr. T. Peter

Bridge, then of NIDA, and was recently published. The

study confirmed that the efficacy and safety of the combined therapy are equivalent to those of buprenorphine

alone and superior to placebo. The combination reduces

craving for and use of opiates, presents limited potential

for abuse, and is suitable for office-based use, the investigators concluded.

14

P

erc

e

nt of Tests O

piate-Fre

e

0

5

10

15

20

25%

Bup Bup/Nal Placebo

17.8

20.7

Treatment Group

5.8

Buprenorphine and 

Buprenorphine/Naloxone Help Patients 

Quit Opiate Abuse

Patients undergoing treatment for opiate addiction who received

buprenorphine or buprenorphine plus naloxone were more likely to

test negative for opiate abuse than patients given placebo. Craving

for opiates also was reduced in the two treatment groups.
Initial Treatment Outcomes

The study began with a double-blind phase in which 323

opiate-addicted individuals (ages 18 to 59) received one of

three treatments for 4 weeks. One group of 109 patients

received tablets totaling 16 mg buprenorphine and 4 mg

naloxone; the second group (105 patients) received tablets

totaling 16 mg buprenorphine only; and the third group

(109 patients) received placebo tablets. All tablets were

identical in appearance and taste. Patients reported to the

clinics for dosing every weekday and took their medications home for weekends and holidays. Study patients and

placebo patients also participated in up to 1 hour of individualized counseling per week. Opiate use was monitored through urine tests every Monday, Wednesday, and

Friday.

The plan for the initial double-blind, 4-week arm of the

study was to recruit 384 patients and provide each patient

with 4 full weeks of therapy. However, recruitment was

halted at 323 subjects because the patients receiving either

medication clearly were doing better than the placebo

patients. Both medication groups showed significant

reductions in opiate use and craving and significant

improvements in perceptions of overall health compared

with those receiving placebo.

In the buprenorphine-naloxone group, the proportion of

opiate-free tests was 17.8 percent; the buprenorphine

group had 20.7 percent opiate-free tests; and the placebo

group, 5.8 percent. The presence of cocaine, the nonopiate drug most commonly found in urine samples in

this study, did not vary significantly among the three

groups. Nor was there a noticeable difference among the

treatment groups in drug-positive results for amphetamines, barbiturates, or methadone.

“The number of urine samples negative for drugs probably would have been higher if investigators had used the

results to counsel patients. Such feedback is known to further reduce patients’ drug use, but that information was

not revealed to the researchers to prevent bias. The urine

test results reflect higher use at the beginning of the

study—when patients are ambivalent about treatment and

in the grip of addiction. It’s positive that opioid use

decreased over the course of the study,” says Dr. Vocci.

Patients in both medication groups also reported reduced

craving for opiates. All groups showed the same average

self-reported craving level before treatment—approximately

60 on a 100-point scale. By week 4 of the study, the average craving scores fell by half for both medication groups

but did not change for the placebo group. Patients receiving medications reported greater improvement in overall

health and well-being than those in the placebo group—

perceptions confirmed by higher weekly clinician ratings

of patients’ overall health and well-being for the two

buprenorphine-treated groups. Because both medications

were clearly effective, the researchers halted the first phase

of the study. Patients receiving placebo during this phase

went on to receive buprenorphine-naloxone combination

treatment in the second phase of the study.

Longer-term Efficacy

The goal of the study’s second phase was to evaluate the

safety of the combination tablet in more natural conditions and over a longer term, without the restrictions associated with the double-blind condition. In this open-label

portion of the study, which lasted up to 52 weeks, all

patients received the combination tablet. Weekly counseling was available along with a daily dose of up to 24 mg

buprenorphine and 6 mg naloxone, tailored to each

patient’s individual response. The sublingual tablet was

administered at the clinic each weekday for the first 2

weeks; after that, patients could take home up to a 10-day

medication supply at the discretion of the investigator.

Of the 472 patients who began this phase of the study,

385 received at least 8 weeks of treatment, and 261 were

treated for at least 6 months. Fourteen patients discontinued therapy because of adverse events, of which detoxification or withdrawal symptoms were the most common.

Opiate-free urine samples in the open-label phase of the

study ranged from 35.2 percent to 67.4 percent in multiple assessments. The overall rate of opiate use was lower

than in the first phase of the study, but cocaine and

benzodiazepine use remained relatively constant, the

researchers reported.

The study concluded that the addition of naloxone to protect against illicit use of the treatment medication did not

reduce the efficacy of buprenorphine. “This new treatment option is historic,” says Dr. Vocci. “Congress passed

the Drug Abuse Treatment Act of 2000 so that buprenorphine products, and other Schedule III, IV, and V medications approved for opioid treatment by FDA, can be prescribed by qualified doctors for the treatment of opioid

addiction. This represents a change to a level of prescribing privileges that American doctors have not had since

the Harrison Narcotic Act of 1914.”

Who Can Benefit

In the two years since the medication was approved, clinicians have gained an understanding of which patients are

most likely to benefit from a take-home treatment option.

Dr. Fudala cautions that buprenorphine is not likely to

work well for every patient. Those less likely to benefit

may include patients who require very high doses of

methadone. Buprenorphine is a partial agonist, which

means that in severely addicted people, it may not provide

enough opiate agonist activity to treat them adequately.

15
Dr. Fudala says the combined agent may be especially useful for patients who do not have extremely high levels of

addiction and for younger individuals, who typically have

a shorter abuse history and may be using smaller amounts

of an addictive substance. “We’re seeing younger and

younger heroin addicts these days,” says Dr. Fudala. “It

may be a good initial treatment for them, either as a medical detoxification or, if necessary, as a longer term treatment. We’ll have a better understanding of this as we gain

more experience.” Another suitable population may be

addicted professionals, including those in health care, who

could be motivated to seek treatment in the privacy of a

physician’s office setting.

Buprenorphine’s suitability for office-based prescribing

is based on its pharmacologic profile. Like methadone,

buprenorphine activates opiate receptors, but its effects

level off as the patient takes higher and higher doses; this

reduces the likelihood of dangerous side effects such as

severe respiratory depression.

The addition of naloxone reduces the potential for abuse

by illicit injection. If a combination tablet is crushed and

injected by a heroin-addicted individual in an attempt to

intensify buprenorphine’s euphoric effect, naloxone kicks

in to induce the symptoms of opiate withdrawal. Finally,

buprenorphine has a relatively long duration of action and

causes comparatively mild withdrawal discomfort on cessation, affording flexibility in dosing regimens and a margin

of convenience for patients and physicians.

As of March 2004, 3,951 U.S. physicians were eligible to

prescribe buprenorphine. Of that group, 2,848 were

granted waivers of a Federal requirement for previous

experience in addiction medicine. This number is growing, according to Dr. Vocci. “We had estimated that about

6,000 physicians would eventually take the training and

get the waiver. So we’re at about 50 percent,” he says. At

this time, he notes, certified physicians are restricted to

treating no more than 30 patients. In October 2005, 3

years from the approval of the new drug combination, the

Department of Health and Human Services and the Drug

Enforcement Administration will evaluate the program

and possibly adjust the restrictions. The overall picture,

however, is positive, says Dr. Vocci. “Very little diversion

has been reported with this new combination,” he says.

Source

• Fudala, P.J., et al. Office-based treatment of opiate

addiction with a sublingual-tablet formulation of

buprenorphine and naloxone. New England Journal of

Medicine 349(10):949-958, 2003.

16
Researchers Adapt HIV Risk Prevention Program for

African-American Women

By Jill Schlabig Williams, NIDA NOTES Contributing Writer

Research Findings

Volume 19, Number 1 (April 2004)

The HIV/AIDS epidemic has taken a disproportionate

toll on racial and ethnic minority populations, especially

women. In its surveillance report on the number of

Americans living with HIV/AIDS in 2002, the Centers

for Disease Control and Prevention estimates that among

women with HIV/AIDS, non-Hispanic African-American

women outnumbered non-Hispanic white women by

three to one—a racial disparity not found among men.

African-American drug-using women were addressed

in two recent studies by NIDA-funded researchers

in Atlanta. Dr. Claire E. Sterk of Emory University,

Dr. Kirk W. Elifson of Georgia State University, and colleagues developed and tested gender-tailored, culturally

specific adaptations of a standard NIDA HIV prevention

intervention. They found that female African-American

injecting drug users (IDUs) and crack cocaine users who

received either of two targeted 4-week prevention programs reduced their risk behaviors related to drug taking

and sex more

than did

women who

received the

standard intervention.

“These studies

are examples

of research

that is responsive to community needs,” says Dr. Dionne Jones of NIDA’s Center

on AIDS and Other Medical Consequences of Drug

Abuse. “When it comes to designing a prevention program, it’s not one-size-fits-all. You have to consider social

context, be culturally sensitive and appropriate, and tailor

your message to the group.”

The researchers’ goal was to develop culturally appropriate programs

grounded in the reality of the daily

lives of women most at risk and the

difficulties they face in their individual, social, family, and sexual

relations and activities. “We worked

hard to develop interventions with

input from this target population,

deliver the interventions in a setting

where they feel comfortable, and

involve them in planning, implementing, and evaluating the interventions,” says Dr. Sterk.

Over 1 year, using one-on-one

interviews and small focus groups,

the researchers sought to define the

key issues in the women’s lives and

identify ways to address those

issues, including such factors as

gender dynamics, economic stressors, gender-specific norms and values, and power and control. Two

interventions came out of this

research phase. One, a motivation

intervention, was designed to motivate the participants to change

17

African-American drug-using women in three intervention groups reduced behaviors that 

heightened their risk of HIV infection. However, women receiving the culturally specific, gendertailored motivation and negotiation interventions generally reported greater reductions in risky

behaviors after their participation than women in the NIDA standard intervention. 

Behavior in 

Past 30 days

NIDA Standard

Intervention Group

Motivation

Intervention Group

Negotiation

Intervention Group

Baseline Six-Month

Followup

Baseline Six-Month

Followup

Baseline Six-Month

Followup

Number of days 

injected powder

cocaine

8.2 3.1 6.4 0.1 4.7 0.2

Number of days 

injected heroin 16.4 8.9 12.7 1.5 9.8 3.2

Percentage who 

traded sex for drugs 70.4 40.7 50.0 20.0 42.9 10.0

Mean number of 

days crack used 17.7 12.9 18.2 15.6 18.7 13.8

Percentage who had 

vaginal sex with 

one or more paying

partners

43.9 24.6 34.3 19.2 30.8 20.5

Injecting Drug Users Crack Cocaine Users

Tailored Interventions Build on NIDA Intervention To Help

Drug-Using Women Reduce HIV Risk
their behavior. The other, a negotiation intervention, recognized that women may fear verbal or physical abuse if

they propose safer sex or safer needle use and thus sought

to strengthen their negotiation and conflict-resolution

skills.

“Our goal in the motivation intervention was to reduce

risk based on what’s realistic in the context of the participant’s life,” explains Dr. Sterk. “We worked with the

women to set short- and long-term goals, celebrate successes, analyze failures, and identify and overcome barriers.” The negotiation intervention recognizes that many of

the women’s challenges dealt with the need to resolve conflict and that negotiation skills are key to reducing risk.

Once the interventions were ready, more than 300

African-American women ages 18 to 59 years—68 IDUs

and 265 crack cocaine users—were enrolled in the studies.

All were HIV-negative and heterosexually active. The

women were randomly assigned to one of the three interventions. The NIDA standard intervention was delivered

in two one-on-one sessions; the motivation and negotiation interventions each involved four one-on-one sessions.

(See textbox, below, for descriptions of each intervention.)

At the 6-month followup, both IDUs and crack cocaine

users in all three groups reported lower levels of drugusing behavior and risky sexual behaviors than they had

reported before receiving the interventions. Reductions

were greater among women who received the tailored

interventions.

Injecting Drug Users. The motivation and negotiation

interventions were equally effective in reducing the incidence of needle and injection-works sharing. At 6 months,

there was no sharing of drug injection paraphernalia in

these groups; in the standard intervention group, 13 percent reported sharing needles and 18 percent reported

sharing injection works. Although women in all intervention groups reduced their number of injections over time,

only those in the tailored interventions reported statistically significant decreases. Participants in the motivation

intervention were most likely to attend drug treatment,

whereas women in the negotiation intervention reported

more changes in their sexual behavior than did women in

other interventions.

Crack Cocaine Users. All three interventions were associated with a drop in crack use in the 30 days preceeding

followup. About 40 percent of the women in each group

reported no use during that period. Among those still

abusing crack at followup, women in the motivation intervention were more likely to have reduced their use of

crack in risky settings, such as outside or in a crack house,

hotel room, or car. Women in the standard and motivation intervention groups significantly decreased the number of paying partners for vaginal sex and the frequency

of sex with paying partners.

Dr. Sterk suggests that the study’s results show it may

be optimal to create an intervention that combines

skills taught in both the negotiation and motivation

18

Protocols for Standard, Motivation, and Negotiation Interventions

All interventions include discussion of the local HIV epidemic, sex and drug-related risk behaviors, safer sex and

drug use, and HIV risk-reduction strategies. The two tailored interventions also include a discussion of the impact of

race and gender on HIV risk and protective behaviors. 

The NIDA standard intervention is an HIV/AIDS education program that was developed in the early 1990s. It

builds on standard HIV testing and counseling developed by CDC and adds discussion of the principles of HIV prevention for drug users and their sex partners. The intervention involves testing, counseling, and educating participants through use of cue cards on such topics as the definition of HIV/AIDS, who is at risk, and ways to reduce

risk. Also offered are demonstrations on condom use and equipment-bleaching techniques for IDUs. Referrals to

counseling and other services are provided.

The motivation intervention follows the format of the standard intervention for the first session but ends with asking participants to consider what they are motivated to change in their lives. During the second session, this list is

reviewed and short- and long-term goals are set. The third and fourth sessions involve discussion of experiences with

behavior change, including the woman’s sense of control and feelings of ambivalence about behavior change. Riskreduction messages tailored to the participant’s level of readiness to change are also delivered in the fourth session.

The negotiation/conflict-resolution intervention also follows the NIDA standard intervention for the first session,

but it ends with a discussion of intended behavior changes. The second session reviews the list of possible behavior

changes and the level of control the participant believes she has and introduces general communication skills and

strategies to develop assertiveness. Short-term goals are set for strengthening communication, gaining control, and

developing assertiveness. Negotiation and conflict-resolution strategies are introduced during the third session and

tailored to the individual during the final session.
interventions. While participants in the negotiation intervention were generally more successful at reducing sexual

risk behaviors, including decreasing the number of paying

partners and increasing condom use with steady partners,

participants in the motivation intervention had more success at changing drug-use behaviors.

Efforts were also made to assist program participants in

their lives outside of the program, with success extending

well beyond the study’s parameters, notes Dr. Sterk. “A lot

of the women who received the one-on-one support available through the tailored interventions said the program

served as a re-entry into society. For example, they were

encouraged to obtain a photo ID. Many reported that this

simple act made them feel more connected to society

again, part of the larger world.” Program graduates

returned to school, earned their GED, found jobs, joined

the project to become counselors or interviewers, and

stopped using drugs.

“Over and over, researchers are finding that we need to

take a more holistic approach to intervention programs,”

says NIDA’s Dr. Jones. “We can’t just focus on drugs and

sex. We must look at the big picture. It involves childcare,

education, employment, housing, and job training.

Community stakeholders need to develop programs

that address multiple needs.”

The project maintained a high retention rate—96 percent of the women enrolled in the studies completed the

6-month followup interview. Dr. Sterk attributes this

success to the fact that the project was grounded in the

community and to the value of involving community consultants—residents, both former drug users and others,

who played key roles in recruiting, interviewing, and

counseling participants.

In future research, Dr. Sterk intends to examine the costeffectiveness of various intervention formats. “It appears

that individual sessions may be more desirable and costeffective,” she predicts. Dr. Sterk would like to continue

the research, assessing the long-term effects of specific

interventions. She wants to develop an intervention that

focuses on women’s households, targeting both the woman

and her main partner, and she is interested in capacitybuilding—translating her research into other settings

and training people to develop similar programs in more

communities.

Sources

• Sterk, C.E.; Theall, K.P.; and Elifson, K.W.

Effectiveness of a risk reduction intervention among

African American women who use crack cocaine.

AIDS Education and Prevention 15(1):15-32, 2003.

• Sterk, C.E.; Theall, K.P.; Elifson, K.W.; and Kidder,

D. HIV risk reduction among African-American

women who inject drugs: A randomized controlled

trial. AIDS and Behavior 7(1):73-86, 2003. 

19

Principles That Guide Format, Content of Interventions

The interventions used by Dr. Sterk and her colleagues in this study are firmly based in theoretical research. The

researchers conducted a series of one-on-one interviews and focus groups with the target population. These interviews yielded the following key principles that guided both the format and the content of the interventions.

• Offer counseling sessions on an individual basis. “It was very clear that women wanted to start with one-onone sessions,” says Dr. Sterk. “HIV risk behaviors involve so many private, personal issues—previous abuse

experiences, actions to support their drug habits, things they’d never before discussed. They found it easier to

discuss these experiences with one person, not a group.”

• Adopt a holistic approach. Along with this research project, a clothing fair was conducted and clothes made

available to program participants. Food for breakfast was provided; daycare was close by; and ongoing services,

such as help preparing for job interviews, were provided. 

• Make programs community-based. The project was headquartered in a house in the community, which was

key to participants’ convenience and comfort. Researchers also found it important for the women to link participation in this project to local social and health services, including local drug treatment, daycare centers, health

services, and other community-based organizations. Community consultants played a key role in the project. 

• Address women’s multiple social roles in the intervention. Participants insisted that they didn’t want to be

labeled simply as drug users. Instead, they wanted the social context of their daily lives to be addressed, including their roles as mothers and steady partners.
New Approaches Seek To Expand Naltrexone Use in

Heroin Treatment

By Robert Mathias, NIDA NOTES Staff Writer

Research Findings

Volume 17, Number 6 (March 2003)

Naltrexone, an opiate treatment

medication, is used to help patients

make the transition from illicit opiate use to a drug-free life. Patients in

naltrexone treatment are first detoxified from their dependence on opiates and then take thrice-weekly

doses of naltrexone and participate

in weekly group therapy sessions.

The medication provides a safety net

for patients because it blocks the

euphoric effects they normally would

feel if they slip and use heroin or any

other opiate. As a result, even relapse, which is common in addiction

treatment, may have a therapeutic

effect as repeated failure to get high

may eventually break the neurobiological and behavioral links between

taking drugs and the rewards that

lead patients to resume regular drug

use. With successful naltrexone treatment, slips to drug use become less

frequent, the medication is discontinued, and patients continue behavioral treatment if needed.

Naltrexone treatment has been successful mainly with

patients who are highly motivated to stop using opiates.

Such patients include health care professionals who must

stop using opiates to retain their licenses to practice medicine and individuals subject to criminal justice sanctions

for relapse to illicit opiate use. The severe penalties that

these patients would incur if they fail treatment enable

them to overcome naltrexone’s main drawback: It eliminates the powerful rewarding effects of opiates without

any replacement to help patients cope with lingering

effects of withdrawal.

Naltrexone’s lack of a reinforcing effect has made it an

unattractive treatment option for other patients who lack

a strong external incentive to stop using drugs and do not

want to go through detoxification and withdrawal from

opiates. Most of these patients opt for treatment with

medications such as LAAM and methadone, both of

which help them to cope with the absence of the intense

and rapid high that they are accustomed to getting from

heroin by replacing it with a more moderate, stabilizing

effect that can help them to maintain a nonaddicted

lifestyle.

Despite its limited clinical use, naltrexone has many qualities that make it an attractive option for treating a broader

range of opiate-dependent patients. It is not addicting, has

few adverse effects, can be prescribed without concerns

about diversion to the illicit drug market, and is not subject to the restrictive regulatory requirements that limit

the use of methadone and LAAM to specialized clinics.

Thus, like the recently approved opiate treatment medication buprenorphine, naltrexone can be administered in

many settings, including private physicians’ offices, making it more attractive to individuals who are reluctant to

enter clinics.

20

0

10

20

30

40

50

60

70

80

90

100%

Standard Naltrexone + CM + SO (Significant Other Involvement) 

Standard Naltrexone + CM (Contingency Management)

Standard Naltrexone Only

0 1 2 3 4 5 6 7 8 9 10 11 12

Subjects Remaining in Treatment

Treatment Week

Source: Archives of General Psychiatry,August 2001.

In a study with 127 heroin-addicted patients receiving naltrexone therapy, the 12-week

dropout rate was about 50 percent among those in two groups that received voucher-based

contingency management, and about 75 percent among those who did not.

Voucher Incentives Increase Retention

In Naltrexone Treatment
Naltrexone’s desirable therapeutic traits have continued to

spark interest in finding new ways to expand its usefulness

and application in practice. Two recent studies show that

adjunctive behavioral and new pharmacological approaches may help to increase naltrexone’s effectiveness for a

wider range of opiate-addicted patients.

Voucher Reinforcement Increases Naltrexone’s

Effectiveness

A NIDA-supported treatment study that rewarded heroindependent patients with vouchers whenever they took

their naltrexone or tested negative for drug use has found

that this basic behavioral reinforcement approach achieved

significantly better results than standard naltrexone

treatment alone in keeping patients in treatment longer,

having them complete treatment, and reducing their opiate use.

“A significant boost in treatment adherence was achieved

not with highly motivated patient groups that have generally responded well to naltrexone treatment, but with predominantly unemployed ‘street addicts,’ most of whom

had a history of extensive involvement with drug abuse

treatment and the legal system,” says Dr. Dorynne

Czechowicz of NIDA’s Division of Treatment Research

and Development. She also maintains that the results are

21

Long-Lasting Formulation Also May Increase

Naltrexone Compliance

NIDA-supported researchers have been testing a long-lasting “depot” formulation of naltrexone that is aimed at

reducing the three-times-a-week frequency with which patients must now take the medication to prevent them from

getting high if they use heroin. The formulation is packaged in microcapsules injected under the skin that slowly

release medication for several weeks. The sustained release of naltrexone is meant to maintain enough medication in

the patient to suppress heroin’s euphoric effects for an extended time.

Clinical trials now under way are assessing the safety and efficacy of depot naltrexone. In a recent trial, Dr. Sandra

D. Comer and a team of researchers from the New York State Psychiatric Institute and Columbia University tested

depot naltrexone in an 8-week inpatient study with 12 heroin-dependent subjects to see how long the medication

remains active in the human body and blocks heroin’s effects. After detoxification, six patients received a low dose

(192 mg) and six received a high dose (384 mg) of the medication. Patients in both groups subsequently were given

a placebo or intravenous heroin once a day from Monday through Friday for 6 weeks. Each week, daily doses of

heroin started at 6.5 mg and increased to 12.5, 18.75, and 25 mg; the placebo was administered randomly on one of

the days.

Researchers assessed subjective, performance, and physiological effects after each dose of heroin or placebo and measured plasma levels of naltrexone over the course of the study. They found that both doses of depot naltrexone substantially suppressed the patients’ ratings of heroin’s pleasurable effects and how much they “liked” the drug and

wanted to take it again. With the high dose of naltrexone, patients’ positive ratings of heroin’s pleasurable effects

remained low for 5 weeks. In the 6th week, ratings increased significantly relative to week one after patients received

the 18.75- and 25-mg injections of heroin. The low dose suppressed positive ratings of heroin for 3 weeks. Plasma

levels of naltrexone remained above 1 ng/mL for 4 weeks with the high dose and 3 weeks with the low dose. Though

these levels are low compared to those resulting from standard naltrexone treatment doses, other studies have reported that even with negligible plasma levels, naltrexone continues to counter heroin’s effects. Other than initial discomfort at the site of naltrexone injection, there were no untoward side effects.

The results suggest that once-a-month administration of the depot formulation can provide safe, long-lasting blockade of the effects of intravenous “streetlevel” heroin doses in patients who have undergone detoxification. Future

studies will address questions that remain about optimal dose levels for naltrexone treatment of heroin dependence,

such as what effects different doses have on withdrawal, craving, and the ability to reduce heroin use.

Source

• Comer, S.D., et al. Depot naltrexone: Long-lasting antagonism of the effects of heroin in humans.

Psychopharmacology 159:351-360, 2002.
promising for expanding the types of patients who would

benefit from naltrexone treatment.

The 12-week study, led by Dr. Kathleen Carroll of the

Yale University School of Medicine, randomly assigned

127 recently detoxified opioid-dependent patients to 1 of

3 treatment conditions: standard treatment with naltrexone 3 times a week; standard naltrexone treatment plus a

behavioral reinforcement approach called contingency

management (CM); or standard naltrexone treatment and

CM plus involvement of a significant other (SO) in up to

6 family counseling sessions. SO treatment was added to

CM for patients in the third group to test the idea that

encouragement and positive reinforcement from a significant other might help patients cope with any protracted

drug withdrawal symptoms and remain in treatment

longer. Patients in all three groups participated in weekly

cognitive-behavioral group counseling sessions.

Patients in the CM groups could earn vouchers, which

they could exchange for goods and services, in separate

tracks for naltrexone compliance or drug-free tests. In

each track, the voucher value started at $0.80, escalated 

in $0.40 increments for continuous compliance or abstinence, and were reset to the starting point for each failure

to take the medication or pass a drug test. Over the course

of the study, patients in the CM groups earned an average

of $189 in vouchers out of the maximum $561 that could

be earned for perfect medication compliance and all negative drug tests.

The researchers found that on average, patients in the two

CM groups stayed in treatment 7.4 weeks, significantly

longer than the 5.6 weeks for those in standard treatment.

A much higher percentage of CM patients also completed

the full 12-week treatment period—47 percent of CM

plus SO patients, 42.9 percent in the CM group, and 25.6

percent of patients in the standard treatment group. These

retention rates with CM added to standard treatment also

compare favorably with rates achieved in previous studies

of standard naltrexone treatment, which have reported

that 60 to 70 percent of patients dropped out of treatment

over a 12-week period, Dr. Carroll notes.

Patients in the CM groups also had significantly better

treatment outcomes than those in the standard naltrexone

group—more days of abstinence, longer periods of continuous abstinence, more opiate-free tests, and a higher percentage of drug-free specimens. Additional analyses suggested CM patients made greater reductions than standard

treatment patients in the frequency with which they used

opiates as the study progressed. Thus, 100 percent of

patients reported weekly opioid use at the beginning of

the study, but fewer than 10 percent of those who completed treatment reported weekly use over the last 4 weeks

of the study. Although adding SO to CM did not improve

most treatment outcomes, further analysis suggested it 

did produce a significant reduction in family problems

over time.

“Our study shows you can really bump up medication

compliance and outcomes with very simple behavioral

interventions,” Dr. Carroll says. “It doesn’t take much

effort or cost for treatment programs to do this, particularly if you look at the potential savings from keeping

patients in treatment longer where they can learn how

not to be drug users.”

Source

• Carroll, K.M., et al. Targeting behavioral therapies to

enhance naltrexone treatment of opioid dependence:

Efficacy of contingency management and significant

other involvement. Archives of General Psychiatry

58(8):755-761, 2001. 

22
Opening the Door to Mainstream Medical Treatment of

Drug Addiction

By Glen R. Hanson, Ph.D., D.D.S., NIDA Acting Director 

Research Findings

Volume 17, Number 5 (January 2003)

The October approval of buprenorphine by the U.S. Food

and Drug Administration for treatment of opiate dependence marks a historic milestone for drug abuse research

and treatment. Buprenorphine crowns more than two

decades of NIDA-supported research on the neurobiology

of drug addiction with a medication that has the potential

to increase the safety, availability, and acceptance of opioid

abuse treatment in the United States.

As the first medication for opioid maintenance treatment

that physicians can dispense in their offices to patients

addicted to heroin and prescription pain relievers,

buprenorphine creates a new therapeutic option whose

convenience and relative privacy should appeal to many

patients and may facilitate the integration of drug abuse

therapy with attention to patients’ other medical needs.

Buprenorphine’s availability culminates the collaborative

efforts of NIDA’s medications development program and

the pharmaceutical division of the firm Reckitt Benckiser.

Over the last decade, these entities conducted clinical trials with more than 2,400 patients that established

buprenorphine’s safety and efficacy in treating opiate

dependence. At the same time, Federal legislators enacted

the Drug Abuse Treatment Act of 2000 (DATA), which

removed numerous regulatory barriers to the use of

approved opiate treatment medications in doctors’ offices.

More than 2,000 physicians already have qualified under

DATA to use buprenorphine in their practices.

Buprenorphine’s distinctive

pharmacology gives it the safety

margin and low potential for

diversion to illicit use required for

office-based use.

Buprenorphine’s distinctive pharmacology gives it the safety

margin and low potential for diversion to illicit use required

for office-based use. The medication’s unique mechanism

of action—how it works to achieve its therapeutic effect

and reduce the likelihood

it will be abused—is

grounded in decades of

basic and clinical research

on the biological and

behavioral underpinnings

of drug addiction.

Using fundamental

knowledge derived from

NIDA-funded research

about where and how

opiates such as heroin

work to achieve their

euphoric effects, NIDA

researchers identified

buprenorphine as a

potential opiate treatment medication in the late 1970s.

Subsequent research with the compound showed that it

interacts in similar but significantly different ways at the

same mu opioid receptor in the brain where heroin, morphine, and prescription pain relievers as well as the treatment medication methadone initiate their effects.

As a partial agonist at this receptor, buprenorphine blocks

heroin’s effects, reduces cravings for the drug, and prevents

unpleasant withdrawal symptoms. Moreover, its potential

for abuse is limited because it produces less stimulation

and physical dependence than full agonist medications,

such as methadone, and its euphoric effect peaks at a

moderate level no matter how much is taken.

NIDA’s medications development program further refined

buprenorphine by developing two formulations for use at

different stages of treatment for opiate addiction. Patients

generally will make the transition from illicit opiate drugs

to Subutex—a medication containing only buprenorphine—in a few days under their physician’s direct supervision when they begin treatment. Once they adjust to

Subutex, patients will be switched to Suboxone, which

contains buprenorphine and an opiate antagonist called

naloxone. This combination of ingredients further reduces

the medication’s potential for illicit injection; if a Suboxone

tablet is crushed and injected in an attempt to accelerate

and intensify buprenorphine’s agonist effects, naloxone

blocks the mu receptor and can induce opiate withdrawal.

Suboxone will be the main prescription medication

23
patients take home for long-term treatment of the physiological changes wrought by chronic opiate abuse, for use

in conjunction with counseling and support services to

help them live stable, productive lives.

Office-based treatment with buprenorphine will give clinicians a powerful new tool to treat opiate addiction; it will

not replace medications now used to treat this disorder.

Much research and clinical experience has shown that

methadone, administered regularly in a comprehensive

treatment program, can reduce or eliminate heroin injection and the attendant risk of AIDS and other infectious

diseases. A longer lasting form of methadone, LAAM (the

first medication developed by NIDA’s medications development program) gives clinicians additional flexibility in

managing opiate dependence. As full agonists at the mu

opioid receptor, both methadone and LAAM address

heroin’s harmful effects but also produce strong physical

dependence and, compared to buprenorphine, have a

higher potential for abuse and greater danger of overdose.

As a result, they remain subject to strict Federal, State, and

local regulations that limit their use to licensed narcotic

addiction treatment clinics.

Methadone clinics will continue to play a crucial role in

treating heroin addiction, but they are able to treat only

one-fifth of the estimated 1 million Americans who are

dependent on opiates. Office-based treatment with

buprenorphine will help fill this treatment gap by providing more treatment options for the 800,000 opiate-addicted individuals not now being treated. People who abuse

heroin or prescription pain medications but have avoided

methadone clinics because of the stigma associated with

them, and likewise, adolescents and young adults who

have become addicted to heroin through snorting the

drug are among the prospective new patients expected to

get the medical help they need from their physicians. In

addition, some stable methadone patients may transfer

from clinic care to office-based treatment to eliminate the

burden of daily methadone clinic visits. As a result of such

transfers, methadone treatment slots will open up for the

many heroin abusers waiting to enter treatment.

The public-private initiatives that have made it possible

for patients to be treated with buprenorphine in their doctors’ offices are based on scientific understanding of drug

addiction as a chronic, relapsing brain disease that can be

treated medically as we treat other chronic diseases, such

as diabetes or hypertension. Office-based treatment with

buprenorphine advances the day when all distinctions

between drug abuse and other medical treatment disappear and primary care physicians and treatment professionals work together to provide patients with the most

effective medications and psychosocial treatments available

for their disease. 

24

Methadone clinics will continue to

play a crucial role in treating heroin

addiction, but they are able to treat

only one-fifth of the estimated

1 million Americans who are

dependent on opiates.
Buprenorphine Approval Expands Options for

Addiction Treatment

Research Findings

Volume 17, Number 4 (November 2002)

Roughly two decades of NIDA-sponsored research and

clinical trials have culminated in the Food and Drug

Administration’s (FDA) approval of buprenorphine as a

treatment for opiate dependence and addiction. The medication was developed through a Cooperative Research

and Development Agreement between NIDA and the

firm Reckitt Benckiser, Inc.

Buprenorphine and the combination buprenorphine/

naloxone are the first medications approved under the

Drug Abuse Treatment Act of 2000 (DATA), which allows

for office-based treatment of opiate addiction. Under the

terms of DATA, physicians providing treatment must

complete special training to dispense the medications,

must agree to treat no more than 30 patients at a time in

an office setting, and must refer patients to appropriate

counseling and support services to enhance pharmacological treatment.

The FDA action will permit physicians to prescribe

buprenorphine as part of office-based practice, making it

possible for patients dependent on heroin or prescription

painkillers such as OxyContin to receive treatment in

their doctors’ offices rather than requiring daily visits

to a centralized methadone clinic. Patients entering or

continuing treatment in clinic settings would also be eligible to receive the new medications. 

The availability of an effective medication that can be

provided in an office-based setting will significantly

increase the number of patients receiving treatment,

according to Dr. Frank Vocci, director of NIDA’s

Division of Treatment Research and Development.

“Nearly 1 million Americans are dependent on opiates,

but only 200,000 of them are getting treatment in

licensed methadone clinics. Approval of this medication

means that many more people who want treatment can

get it,” Dr. Vocci says. “FDA approval of this medication marks a truly great moment in the treatment of

drug dependence and addiction, and it clearly shows the

value of collaborative partnerships between legislators,

Federal agencies, and private industry.”

Buprenorphine is pharmacologically related to morphine

and is a partial opioid agonist—it has the same effect on

mu opiod receptors in the brain as does heroin or other

25

“We are hopeful bupenorphine will be the first of many

new drug addiction medications eligible for use under the

Drug Abuse Treatment Act of 2000 legislation.”

—Senator Orrin Hatch (R-Utah), 

coauthor of DATA.

“Approval of this new drug will allow for the long-awaited

and appropriate conventional, office-based approach to

addiction treatment in this country.”

—Senator Carl Levin (D-Michigan), 

coauthor of DATA.
opiate drugs, but it has a lower maximum effect. Buprenorphine reduces or eliminates withdrawal symptoms

associated with opioid dependence but is not strong

enough to produce the euphoria and sedation caused by

heroin or other opiates. Increasing the dose of buprenorphine does not enhance the drug effects, however, so the

medication is unlikely to be abused.

FDA approved two forms of the medication. Buprenorphine alone will be prescribed (under the trade name

Subutex) for patients in the early stages of treatment.

Buprenorphine combined with naloxone, an opioid

antagonist, will be prescribed (as Suboxone) for long-term

maintenance therapy that will allow patients to resume

and maintain normal, productive lives during treatment.

Combining the antagonist naloxone with buprenorphine

further reduces the potential that the medication could be

abused; injecting the combined formulation triggers withdrawal symptoms. Subutex and Suboxone will be provided

in tablet form as take-home medications. 

26
Research Findings

27

Combining Medications May Be Effective Treatment for

“Speedball” Abuse

By Kimberly R. Martin, NIDA NOTES Contributing Writer 

Volume 17, Number 3 (October 2002)

NIDA-supported researchers from Harvard Medical

School-McLean Hospital, in Belmont, Massachusetts, discovered that a combination of the drugs buprenorphine

and indatraline reduced the self-administration of “speedball” by monkeys. Speedball is a cocaine-heroin mixture

that is taken by some injecting drug users and may

increase the adverse consequences of drug abuse, such as

greater severity of psychiatric disorders, higher incidence

of failure in drug abuse treatment, and increased risk of

contracting HIV infection.

Speedball abuse presents special challenges for drug abuse

treatment. Cocaine and heroin exert different effects on

the brain, and little is known scientifically about how the

two drugs interact. Current medications for heroin abuse,

such as methadone, are only moderately effective in reducing speedball abuse and at present there are no effective

medications for cocaine abuse. Combinations of medications that target the effects of either cocaine or heroin

have shown promise in reducing speedball self-administration in preclinical studies.

“Clinical experience has shown that the most effective

medications currently available to treat drug abuse have

two distinguishing characteristics,” said co-investigator

Dr. Nancy K. Mello. “First, these medications produce

behavioral effects that are similar to the abused drug

and minimize or prevent withdrawal symptoms. Second,

these medications have a slow onset and long duration

of action, resulting in a lower potential for abuse than

rapid-onset, short-acting drugs such as heroin or cocaine.

Indatraline, a dopamine reuptake inhibitor, and buprenorphine, an opioid mixed agonist-antagonist, each meet

both of these criteria. Both drugs have a long duration of

action; buprenorphine produces behavioral and physiological effects similar to heroin; indatraline is an experimental

drug that produces cocaine-like effects.”

Dr. Mello and Dr. S. Stevens Negus compared the effects

of chronic treatment with indatraline and buprenorphine

separately and in combination on speedball self-administration by rhesus monkeys. Five monkeys previously

trained to self-administer cocaine were given access to

speedball combinations (3:1 ratios of cocaine to heroin),

which they began to self-administer more than 70 times

a day.

Over four 10-day periods, the monkeys were treated daily

with saline, with indatraline or buprenorphine alone, and

with the indatraline-buprenorphine combination in three

increasing concentrations. Saline and the lowest concentration of the combined medications had little effect on

speedball self-administration; the highest doses of the

combined medications significantly decreased the number

of times the monkeys self-administered speedball.

By the fifth day of treatment with a combination of indatraline and buprenorphine, speedball injections decreased

by more than 90 percent, to fewer than five injections per

day in four of the five monkeys studied. The same doses

of indatraline or buprenorphine alone did not significantly

reduce speedball self-administration.

Indatraline-Buprenorphine Combination

Reduces Self-Injection of Speedball

by Monkeys

80

60

40

20

0

1 2 3 4 5 6 7 8 9 10

Consecutive Days

Speedball* Injections/Day *Speedball: Cocaine 0.01 + heroin 0.0032 mg/kg/inj

0.32 + 0.01 mg/kg/day

0.56 + 0.18 mg/kg/day

Before treatment with a combination of indatraline and buprenorphine, monkeys injected speedball an average of 66 to 78 times per

day. After treatment, speedball self-administration was reduced

and the decreases were sustained throughout 10 days of treatment.

After 5 days of treatment with the highest dose of the combined

medications, speedball self-administration decreased to between

zero and five injections per day.
28

“The combination of indatraline and buprenorphine not

only reduced speedball self-administration, but these

effects were sustained across the 10-day treatment period

and over a range of doses,” says Dr. Mello. “These findings underline the importance of exploring medication

combinations as a novel approach for treatment of polydrug abuse.”

“Although this study used an animal model, the results are

intriguing and suggestive of potential clinical efficacy,”

said Dr. Jane Acri of NIDA’s Division of Treatment

Research and Development. “There is evidence that

buprenorphine can reduce opiate use in humans, but the

data supporting the use of compounds such as indatraline

for reducing cocaine use by humans are more limited. The

selection of a combination mechanism strategy is reasonable; further study is needed to determine the effectiveness

of these compounds in the treatment of speedball abuse in

humans.”

Sources

• Mello, N.K., and Negus, S.S. Effects of flupenthixol

and quadazocine on self-administration of speedball

combinations of cocaine and heroin by rhesus monkeys. Neuropsychopharmacology 21:575-588, 1999. 

• Mello, N.K., and Negus, S.S. Effects of indatraline

and buprenorphine on self-administration of speedball combinations of cocaine and heroin by rhesus

monkeys. Neuropsychopharmacology 25(1):104-117,

2001. 
Research Findings

29

High-Risk Sex Is Main Factor in HIV Infection for Men and Women

Who Inject Drugs

By Robert Mathias, NIDA NOTES Staff Writer 

Volume 17, Number 2 (May 2002)

A 10-year study has found that the

biggest predictor of HIV infection

for both male and female injecting

drug users (IDUs) is high-risk sexual

behavior, not sharing needles used to

inject drugs. High-risk homosexual

activity was the most important factor in HIV transmission for men;

high-risk heterosexual activity was

most significant for women. Risky

drug-use behaviors also were strong

predictors of HIV transmission for

men but were less significant for

women, the study found.

“In the past, we assumed that IDUs

who were HIV-positive had been

infected with the virus through

needle-sharing,” says Dr. Steffanie

Strathdee of the Johns Hopkins

University Bloomberg School of

Public Health in Baltimore, who

conducted the NIDA-funded study.

“Our analysis indicates that sexual

behaviors, which we thought were

less important among IDUs, really

carry a heavy weight in terms of

risks for HIV seroconversion for

both men and women.” 

In the study, Dr. Strathdee led a

team of researchers who analyzed data collected every 6

months from 1,800 IDUs in Baltimore from 1988 to

1998. Participants had to be at least 18 years of age when

they entered the study, have a history of injection drug use

within the previous 10 years, and not have HIV infection

or AIDS. More than 90 percent of the participants said

they had injected drugs in the 6 months prior to enrolling

in the study. In their semi-annual interviews, study participants reported their recent drug use and sexual behavior

and submitted blood samples to determine if they had

become HIV-positive since their last visit.

Researchers analyzed the role of homosexual activity in

HIV seroconversions among male IDUs in the study, after

taking into account other factors that increased their risk

of acquiring HIV, such as their drug injection practices.

This analysis revealed that the incidence of HIV infection

among male IDUs who had engaged in homosexual activity within the previous 6 months was 10.44 percent a year,

compared to 3.01 percent among men who did not report

having homosexual sex.

Visiting “shooting galleries,” where drug abusers gather to

obtain and inject drugs, sharing needles used to inject

drugs with multiple partners, and injecting drugs daily

also were independently linked to significantly higher rates

of HIV infection among men in the study. Men who said

they had used shooting galleries had an HIV incidence

rate of 6.28 percent per year, and men who shared needles

with more than one partner had a rate of 5.52 percent

per year. These infection rates were more than double

those found among men who had not engaged in these

High-Risk Sexual Behavior Leading 

Cause of HIV Infection Among Injection 

Drug Users in 10-Year Study

0

2

4

6

8

10

12

Any 

STD

Used 

Shooting

Galleries

Shared 

Needles

Homosexual 

Activity

Used 

Shooting 

Galleries

Shared 

Needles

Men Women

Annual Rates of HIV Infection

4.53%

6.28%

10.4%

4.35% 4.73%

8.13%

High-risk sexual behavior played the biggest role in HIV infection for both male and female

injection drug users (IDUs) in this study of 1,800 IDUs. Significant risk factors for men were

high-risk homosexual activity, using shooting galleries, and sharing needles used to inject drugs

with multiple partners. For women, high-risk heterosexual activity, as indicated by reporting a

recent sexually transmitted disease (STD), was the most significant cause of HIV infection. 
30

behaviors. Men who injected drugs at least once a day had

HIV infection rates of 4.68 percent, more than one and

one-half times the rate among men who had injected less

than once a day.

Sharing needles also increased risk of HIV infection

among women IDUs. However, high-risk heterosexual

activity was a much more important risk factor for these

women, the study found. In fact, other than being

younger than 30 years—which independently predicted

HIV infection for both sexes—high-risk heterosexual

activity was the main predictor of HIV seroconversion

among women. Women who reported having a recent

sexually transmitted disease (STD), an indicator of unprotected sex, had more than 2.5 times the rate of HIV infection of women who did not have an STD.

“Both homosexual men and heterosexual women IDUs

appear to be at dual risk for becoming infected with

HIV,” Dr. Strathdee says. “In previous studies by our

group, being a gay male IDU was closely linked to visiting

shooting galleries and sharing needles. Heterosexual

women IDUs tend to have more of an overlap in their

sexual partners and their drug use than men do. This puts

them at increased HIV risk because they are sharing needles and having unprotected sex with a partner who is

more likely to be infected with the virus.”

“HIV prevention programs have done a good job in

reducing needle-sharing and other drug-use behaviors that

spread the virus among IDUs,” Dr. Strathdee says.

“However, our study indicates that HIV prevention programs can achieve better results by also addressing sexual

risk behaviors among IDUs. A multifaceted approach is

needed that screens both men and women IDUs for STDs

at places where they go, such as needle-exchange programs

and methadone treatment programs, and provides comprehensive treatment at those sites.”

“HIV prevention efforts also should be gender-specific,

targeting the important differences we have found in sexual and drug-use behaviors among men and women that

increase their risk of acquiring and transmitting HIV,” Dr.

Strathdee says. “For example, women IDUs in stable relationships could be shown how to negotiate condom use

with their partners and offered couple counseling to educate both partners about HIV risks associated with their

drug use and sexual behaviors. We need more research to

identify and evaluate HIV prevention approaches for male

IDUs who have sex with men to determine what kinds of

interventions might work.”

Source

• Strathdee, S.A., et al. Sex differences in risk factors for

HIV seroconversion among injection drug users.

Archives of Internal Medicine 161:1281-1288, 2001.
31

Buprenorphine Taken Three Times per Week Is as Effective as Daily

Doses in Treating Heroin Addiction

By Patrick Zickler, NIDA NOTES Staff Writer

Research Findings

Volume 16, Number 4 (October 2001)

Buprenorphine, a medication developed through NIDAfunded research, has been shown in clinical trials to be

an effective treatment for opioid addiction when taken

in daily doses. Research at Yale University School of Medicine in New Haven, Connecticut, now suggests that

buprenorphine taken three times per week is similarly

effective. This finding, says NIDA-supported investigator

Dr. Richard Schottenfeld, makes buprenorphine an even

more flexible alternative to methadone, a medication that

has been used for decades to treat opioid addiction.

Methadone is the most widely used medication for opioid

addiction, yet fewer than one in five heroin users now

receive methadone treatment for their addiction, Dr.

Schottenfeld says. A daily dosing requirement and distressing symptoms of withdrawal that can result from a missed

dose cause some heroin users to drop out of or to forgo

methadone treatment programs. “Buprenorphine has relatively mild withdrawal symptoms, and a treatment schedule that does not require daily dosing could significantly

increase the number of heroin users seeking treatment

when buprenorphine becomes available,” he says.

Buprenorphine is in the final stages of the Food and

Drug Administration (FDA) approval process.

Dr. Schottenfeld and his colleagues compared the effectiveness of daily versus thrice-weekly administration of

buprenorphine in a 12-week trial involving 92 participants (73 percent white, 75 percent male) who met diagnostic criteria for opioid dependence and FDA criteria for

eligibility in methadone maintenance treatment, but who

were not currently in treatment. Forty-five participants

were assigned to receive daily buprenorphine in an average

daily dose of 16 mg per 70 kg of body weight. Forty-seven

participants received doses of 34 mg per 70 kg of body

weight on Fridays and Sundays, 44 mg per 70 kg of body

weight on Tuesdays, and a placebo on other days. All 92

study participants provided urine samples on Mondays,

Wednesdays, and Fridays. All samples were analyzed for

opioids and cocaine metabolites, and one sample per week

from each participant was tested for benzodiazepines.

“There were no significant differences between groups in

reduction of opioid use, in retention in the treatment program, or in cocaine use,” Dr. Schottenfeld says. “Interviews with the participants suggest that they couldn’t reliably tell whether they were receiving the medication daily

or three times each week.”

Roughly three-quarters of the participants (77 percent of

those receiving thrice-weekly and 71 percent of those

receiving daily medication) completed the full 12-week

program. The proportion of opioid-positive urine samples

dropped consistently through the course of treatment (to

57 percent in the daily and 58 percent in the thrice-weekly group), and participants in both groups reported substantial reductions in illicit drug use. The similarity in

drug use is evidence that the participants felt no stronger

urge to use opioids than those on the daily schedule, Dr.

Schottenfeld says. Equally important, he notes, is the fact

that both groups were equally likely to stay in treatment,

to show up on time for treatment, and to attend regularly

scheduled counseling sessions.

In this study, all participants made daily clinic visits even

though the thrice-weekly group received medication only

every third day. Additional research is needed to determine the effectiveness of thrice-weekly dosing on a schedule that does not require daily contact, Dr. Schottenfeld

says. Still, he adds, the finding that thrice-weekly dosing

can be as effective as daily dosing in treatment outcome is

an important step forward that builds on previous research

indicating that some patients would prefer less-than-daily

dosing of medication.

Patients in treatment for opioid addiction received either daily 

or thrice-weekly doses of buprenorphine. Both groups showed 

reductions in reported days of heroin use during a 13-week 

treatment program. 

Daily or Thrice-Weekly Buprenorphine Doses Yield

Similar Declines in Days of Drug Use
32

“This schedule of treatment could substantially reduce the

cost to clinics and the inconvenience to patients. It can

also help move use of buprenorphine beyond the traditional narcotic treatment programs and into new treatment settings, such as primary care clinics or physicians’

offices,” Dr. Schottenfeld says.

Source

• Schottenfeld, R.S.; Pakes, J.; O’Conner, P.; Chewarski,

M.; Oliveto, A.; and Kosten, T.R. Thrice-weekly versus daily buprenorphine maintenance. Biological

Psychiatry 47(12):1072-1079, 2000. 
Research Findings

33

33-Year Study Finds Lifelong, Lethal Consequences of 

Heroin Addiction

By Patrick Zickler, NIDA NOTES Staff Writer

Volume 16, Number 4 (October 2001)

Heroin addiction exacts a terrible toll. For many addicts

the condition lasts a lifetime—a lifetime shortened by

health and social consequences of addiction. NIDA-supported researchers at the University of California, Los

Angeles (UCLA), examined the patterns and consequences

of heroin addiction over 33 years in nearly 600 heroinaddicted criminal offenders and found that their lives were

characterized by repeated cycles of drug abuse and abstinence, along with increased risk of crime or incarceration,

health problems, and death.

Drs. Yih-Ing Hser, Valerie Hoffman, Christine Grella, and

Douglas Anglin of UCLA’s Drug Abuse Research Center

studied a group of 581 male heroin addicts admitted

between 1962 and 1964 to the California Civil Addict

Program (CAP), a compulsory drug treatment program

for criminal offenders. By 1997, nearly half of the group

had died, roughly 40 percent of those still living reported

using heroin within the past year, and fewer than 10 percent of the survivors were currently enrolled in methadone

treatment.

The death rate among the members of the group is 50 to

100 times the rate among the general population of men

in the same age range. “The high mortality rate is evidence of the severe consequences of heroin use,” Dr. Hser

says. “Even among surviving members of the group, severe

consequences such as high levels of health problems, criminal behavior and incarceration, and public assistance were

associated with long-term heroin use.”

Researchers first interviewed the participants during the

period 1962 through 1964 and conducted followup interviews at roughly 10-year intervals–in 1974 and 1975,

1985 and 1986, and 1996 and 1997. In the most recent

interviews, the UCLA researchers found that 284 (49 percent) of the 581 addicts enrolled in CAP between 1962

and 1964 had died. The most common cause of death

(21.6 percent) was accidental poisoning or drug overdose.

Homicide, suicide, or accident accounted for 19.5 percent

of deaths, and the next most common causes were liver

disease, cancer, and cardiovascular diseases (15.2, 11.7,

and 11.7 percent, respectively). Fifty-five original participants could not be located, refused to be interviewed, or

could not be interviewed.

Of the 242 surviving members interviewed in 1996 and

1997, 135 (55.8 percent) were not currently using heroin,

50 (20.7 percent) were actively using heroin, and 23 

(9.5 percent) refused to provide urine samples for testing.

In addition, urine samples were not available from 34 men

who were incarcerated at the time of the interviews.

During any given year, roughly 10 percent of participants

were in treatment, according to Dr. Hser. “Although many

of the survivors reported that they had been able to stop

using heroin for extensive periods, fewer than half reported abstinence for periods of more than 5 years,” Dr. Hser

During interviews conducted in 1996 and 1997, heroin abusers

who had been continuously abstinent for at least the last 5 years

were less likely than other abusers to have used other drugs in the

past year. 
34

says. “Abstinence for 5 years significantly reduced the likelihood of relapse, but even among those who achieved 15

years of abstinence, a quarter still relapsed.” Those who

achieved abstinence for more than 5 years were more likely to be employed and less likely to report that they had

health problems that prevented them from working, were

receiving public assistance, or had been involved in criminal activity than were the rest of the cohort. Rates of HIV,

hepatitis, and sexually transmitted diseases did not differ

very much between those who had achieved more or less

than 5 years of abstinence.

Dr. Hser adds that the results of the 33-year followup

study should be considered in light of the fact that all

members of the study originally were selected from a corrections-based treatment program and may not be representative of addicts who would have voluntarily sought

treatment in community-based facilities had those programs been available 30 years ago. “Nevertheless, we

believe the findings on patterns of heroin use and related

consequences have important implications for the study of

heroin addicts generally,” Dr. Hser says. “These results

suggest that heroin addiction treatment programs should

prepare addicts for the fact that relapse is a very real possibility. Most people go into treatment thinking that they

will be cured and not return to addiction, but abstinence

is very difficult to maintain.”

Heroin addicts and treatment providers should understand

that treatment is a way to achieve abstinence and that

recovery consists of improvements resulting from those

periods when they are free of addiction, Dr. Hser says.

Source

• Hser, Y-I.; Hoffman, V.; Grella, C.E.; and Anglin,

M.D. A 33-year follow-up of narcotics addicts.

Archives of General Psychiatry 58(5):503-508, 2001.
Research Findings

35

Buprenorphine Proves Effective, Expands Options For Treatment of

Heroin Addiction

By Josephine Thomas, NIDA NOTES Contributing Writer 

Volume 16, Number 2 (May 2001)

NIDA-supported researchers continue to expand treatment options for heroin addicts. A recent clinical trial

showed that buprenorphine can be as effective as levoalpha-acetyl-methadol (LAAM) and high-dose methadone

in the treatment of heroin addiction. All three of these

medications are more effective than low-dose methadone.

Dr. Rolley Johnson of The Johns Hopkins University in

Baltimore led the research team that compared the different types of opioid addiction treatment medications. The

team randomly assigned 220 heroin-addicted volunteers

between the ages of 21 and 55 to 1 of 4 treatments: 16 to

32 mg of buprenorphine 3 times a week; 75 to 115 mg of

LAAM 3 times a week; high-dose (60 to 100 mg daily)

methadone; or low-dose (20 mg daily) methadone.

Treatment effectiveness was measured through participants’ reports of heroin use, medication and drug levels in

participants’ urine samples, and how long participants

remained in the study. Participants in the buprenorphine,

LAAM, and high-dose methadone groups who completed

the study reported that their heroin use decreased 90 percent on average. Urine tests conducted 3 times a week

revealed that LAAM produced the longest period of abstinence; 36 percent of these patients had 12 consecutive

heroin-free urine samples. A total of 26 percent of

buprenorphine and 28 percent of high-dose methadone

patients, but only 8 percent of the low-dose methadone

patients, had 12 consecutive negative tests. Overall, 50.9

percent of the study’s participants completed the 17-week 

study. The retention rates ranged from a high of 72.7 percent in the high-dose methadone group to 58.2 percent in

the buprenorphine group, 52.7 percent in the LAAM

group, and 20 percent in the low-dose methadone group.

“This study illustrates that there is more than one alternative for the effective treatment of heroin addiction,” says

Dr. Frank Vocci, director of NIDA’s Division of Treatment Research and Development. “Although methadone

remains the ‘gold standard,’ the new medications do not

have to be administered in public clinics and closely

supervised in the way high-dose methadone administration has been in the past. The results of this research thus

open the door to medical mainstreaming—treatment in

doctors’ offices and private facilities, rather than only in

narcotic treatment programs—for

individuals addicted to heroin.”

“This research demonstrates that

these three medications are effective for the treatment of heroin

addiction and that a one-size-fitsall model is no longer necessary,”

says Dr. Johnson. “Future

research will help clinicians identify which patients will benefit

most from which medications.

“Heroin addiction is a chronic

brain disease, and we can treat it

like any other chronic medical

condition—considering alternatives for treatment and planning

that treatment based on individual patient needs,” Dr. Johnson continues. “Since it is difficult to have this kind of medical model of treatment

with only one medication, expanding the numbers and

types of potential treatment medications should help

bring the treatment of opiate addiction into mainstream 

medical practice.” 

Source

• Johnson, R.E., et al. A comparison of levomethadyl

acetate, buprenorphine, and methadone for opioid

dependence. New England Journal of Medicine

343(18):1290-1297, 2000. 

Buprenorphine proved as effective as LAAM and high-dose methadone in treating patients

addicted to heroin. All three medications were more effective than low-dose methadone.
Research Findings

36

Nicotine Craving and Heavy Smoking May Contribute to Increased

Use of Cocaine and Heroin

By Patrick Zickler, NIDA NOTES Staff Writer 

Volume 15, Number 5 (October 2000)

People who abuse drugs are also likely to be cigarette

smokers. More than two-thirds of drug abusers are regular

tobacco smokers, a rate more than double that of the rest

of the population. NIDA researchers have found that craving for nicotine appears to increase craving for illicit drugs

among drug abusers who also smoke tobacco, and this

relationship suggests that smokers in drug treatment 

programs may be less successful than nonsmokers in 

staying off drugs.

At NIDA’s Intramural Research Program in Baltimore, Dr.

Stephen Heishman and his colleagues examined the interaction of craving for nicotine and craving for other drugs

and found that situations that increased desire to smoke

also increased desire to use drugs. The study involved male

and female adult smokers who were not trying to stop

smoking and had histories of abusing alcohol, cocaine,

heroin, marijuana, and/or other substances.

The researchers asked participants to listen to recorded

scripts describing scenes and then to rate their urge to

smoke and their desire to use other drugs. In the first part

of the study, which involved 18 participants, the scripts

had content that was generally pleasant (watching children

on a sunny beach), unpleasant (a friend asking to borrow

money), or neutral (doing household chores). Some scripts

also included people expressing a desire to smoke, while

others did not mention smoking at all (see “Cues Trigger

Craving”). Both the scripts including a mention of smoking and those containing negative emotional content

increased the participants’ craving for drugs, as well as 

for smoking.

In the second part of the study, 24 participants heard

scripts with only pleasant content (enjoying the beach,

talking on the phone with an old acquaintance, or visiting

friends). These scripts also contained descriptions of

tobacco craving that increased in intensity from no mention of smoking to asking the question, “How could you

really enjoy yourself fully unless you were smoking?”

Participants reported that craving for both drugs and

tobacco increased as the intensity of the tobacco craving

messages in the scripts increased.

“One of our more interesting findings was that scripts that

elicited craving for tobacco also elicited craving for the

subject’s drug of choice. This suggests that real-world situations that produce tobacco craving also may result in

craving for drugs of abuse,” Dr. Heishman says. The findings also suggest that treatment for heroin, cocaine, or

alcohol addiction might be more effective if it included

concurrent treatment of tobacco addiction, he says.

In a NIDA-supported study at the University of

California, San Diego, doctoral candidate Dominick

Frosch and his colleagues at the Integrated Substance

Abuse Program at the University of California, Los

Angeles, investigated the relationship between levels of

cigarette smoking and levels of cocaine and heroin use

among 32 individuals who had been in a methadone

treatment program for at least 4 months. The participants

included 10 nonsmokers (6 female, 4 male) and 22 smokers (16 female, 6 male). The smokers were equally divided

among heavy smokers (20 to 40 cigarettes per day) and

“chippers” who smoked 5 or fewer cigarettes per day. 

Among patients in a methadone

treatment program for opiate

addiction, levels of cocaine or

opiate use were directly related to

levels of cigarette smoking.

Cigarette Smoking Associated With Use of Cocaine and Opiates
37

“Compared with heavy smokers, chippers have less intense

craving for their first cigarette of the day and can more

comfortably avoid smoking in situations where it is not

permitted,” Mr. Frosch explains.

The researchers evaluated the connection between tobacco

smoking and illicit drug use among the smokers and nonsmokers by using breath and urine samples from the participants over a 7-day period. They found that the amount

of cocaine and heroin use was closely related to the level

of tobacco use. “The more cigarettes smoked, the more

likely the person was to use illegal drugs,” Mr. Frosch says.

“These findings provide compelling reasons for implementing smoking cessation programs for patients in

methadone treatment, as the benefits of smoking cessation

may extend to opiate addiction as well.” 

Sources

• Taylor, R.C.; Harris, N.A.; Singleton, E.G.;

Moolchan, E.T.; and Heishman, S.J. Tobacco craving:

intensity-related effects of imagery scripts in drug

abusers. Experimental and Clinical Psychopharmacology

8(1):75-87, 2000.

• Frosch, D.L.; Shoptaw, S.; Nahom, D.; and Jarvik,

M.E. Associations between tobacco smoking and illicit drug use among methadone-maintained opiatedependent individuals. Experimental and Clinical

Psychopharmacology 8(1):97-103, 2000. 

Cues Trigger Craving

To evaluate the impact of the urge to smoke on craving for other drugs, Dr. Stephen Heishman and his colleagues

asked participants to rate their desires for tobacco and other drugs after listening to recorded “scripts” of scenes

involving pleasant, unpleasant, or neutral situations and containing “urge” or “no-urge” smoking cues. The scripts

were originally developed by Dr. Stephen Tiffany and colleagues at Purdue University. 

Pleasant, no-urge script: You’re at the beach, lying on a blanket. The warm sun penetrates your skin and relaxes you

thoroughly. A fresh breeze blows over your body as you run your hands through the clean white sand and let the

grains fall through your fingers. You’re feeling refreshed and at ease, and pleasant thoughts run through your mind.

You can hear the sound of waves splashing rhythmically against the shore. Nearby there are some children playing a

game. A bright red beach ball lands near your blanket. You look up and see two of the children running toward you

to get their ball. You stand up, pick up the ball, and toss it to them. They laugh and giggle and run back to their

game. You go to the blanket and lie down. You’re enjoying this day completely. 

Pleasant, urge script: You’re at a friend’s house sitting in a big comfortable chair. You’re with people you’ve known a

long time, and you’re enjoying yourself very much. You’re sipping a drink, and you’re feeling totally at ease. Many of

your friends are smoking cigarettes, just as you used to do. You’ve gone an entire week without smoking. As you sit

there listening to the conversation and laughter, you begin to wonder what a cigarette would taste like. The more

you think about smoking, the stronger your desire becomes. Maybe just tonight when you’re with your friends and

having a good time, it would be okay to smoke. How could you really enjoy yourself fully unless you were smoking?

Your desire to smoke becomes intense, and you know that there’s no good reason not to ask one of your friends for a

cigarette.

Sources

Tiffany, S.T., and Drobes, D.J. Imagery and smoking urges: the manipulation of affective content. 

Addictive Behavior 15(6):531–539, 1990.

Tiffany, S.T., and Hakenwerth, D.M. The production of smoking urges through an imagery manipulation: 

psychophysiological and verbal manifestations. Addictive Behavior 16(6):389–400, 1991.
Research Findings

38

Drug Abuse Treatment Programs Make Gains in Methadone

Treatment and HIV Prevention

By Steven Stocker, NIDA NOTES Contributing Writer 

Volume 15, Number 3 (August 2000)

Drug abuse treatment programs have substantially

improved their methadone treatment practices and

increased their HIV prevention efforts since the late

1980s, according to recent NIDA-funded research. These

improvements appear to be partly the result of NIDA’s

efforts to improve drug abuse treatment and HIV/AIDS

outreach.

Clinical studies conducted in the late 1980s and early

1990s indicated that methadone treatment is more likely

to reduce heroin use if the dose level is at least 60 milligrams per day (mg/day), if patients are given a voice in

determining their dose levels, and if no restriction is

placed on treatment duration. Subsequent research, however, indicated that the majority of the Nation’s

methadone treatment facilities were dispensing methadone

doses less than 60 mg/day, were not giving patients a voice

in dosage decisions, and were encouraging patients to stop

taking methadone in 6 months or less.

In response to this situation, NIDA and other Federal

agencies took steps to improve methadone treatment.

NIDA funded an Institute of Medicine report that recommended changes in heroin addiction treatment practices

and their regulation. NIDA also funded the development

of a quality assurance program that evaluates methadone

treatment facilities in terms of patient outcomes. In addition, the Center for Substance Abuse Treatment (CSAT)

developed a set of methadone treatment guidelines and

distributed them to State substance abuse agencies and

treatment providers around the country.

To determine whether these efforts were in fact improving

methadone treatment practices, in 1995 Dr. Thomas

D’Aunno of the University of Chicago and his colleagues

at the University of Michigan in Ann Arbor collected data

from 116 methadone treatment facilities located throughout the country and compared them with data collected

on these same facilities in 1988 and 1990. Results showed

improvement during the 7-year period, particularly

regarding methadone dosage. The average dose was 45

mg/day in 1988 and 46 mg/day in 1990. By 1995, however, the average dose had increased to 59 mg/day. Also,

more programs were allowing patients to participate in

dosage decisions, and more programs were waiting at

least a year before encouraging patients to stop taking

methadone.

“Although these results show that methadone treatment

facilities have made substantial improvements, we still

need to make more progress,” says Dr. D’Aunno. “We

found an average dose of 59 mg/day in our sample of

treatment facilities, but recent research indicates that 

doses between 80 and 100 mg/day may be the most 

effective in reducing heroin use.” (See “High-Dose

Methadone Improves Treatment Outcomes” on page 

41 of this collection.)

The study found differences in treatment practices in different areas of the country and for different population

groups. Dr. D’Aunno suggests that efforts targeted at particular groups of programs may be a further step to

improve treatment.

Dr. Bennett Fletcher of NIDA’s Division of Epidemiology,

Services, and Prevention Research agrees that efforts to

improve methadone treatment practices should continue

but adds that misunderstandings some patients have about

methadone may also contribute to the problem. For example, he says, some patients attribute adverse effects to

methadone that it actually does not cause. “These patients

may develop medical or dental problems while taking

heroin, but they don’t notice them either because of heroin’s analgesic effect or because they are distracted by withdrawal symptoms during abstinence,” he says. “Once

they’re in methadone treatment and physiologically stabilized, the medical or dental problems are unmasked. It is

easy to blame methadone for these problems, when in fact

they were pre-existing.” These misunderstandings may

cause some patients to request lower methadone doses or

to stop methadone prematurely, says Dr. Fletcher.

The treatment facilities most likely to

conduct HIV prevention activities were

those that had more patients at high

risk of HIV infection, more resources,

and lower patient-to-staff ratios. 
39

The Bandwagon Effect

Dr. D’Aunno, along with colleagues at the University of

Iowa in Iowa City and the Centers for Disease Control

and Prevention in Atlanta, also evaluated treatment facilities’ HIV prevention efforts, including HIV testing, counseling, and outreach. For this project, they used data collected from the sample of methadone treatment facilities

plus other substance abuse treatment facilities for a total

of 618 facilities.

As with the methadone treatment practices, the investigators found that the facilities had made substantial

improvements in their HIV prevention efforts over the

period from 1988 to 1995. In both 1988 and 1990, only

39 percent of the facilities provided HIV testing and

counseling, but by 1995, 61 percent were providing these

services. Also, 51 percent of the facilities in 1988 and 65

percent in 1990 were engaging in HIV outreach, but by

1995 this had increased to 75 percent.

The investigators found that the treatment facilities most

likely to conduct HIV prevention activities were those

that had more patients at high risk of HIV infection,

more resources, and lower patient-to-staff ratios. Also,

these facilities generally were publicly rather than privately

funded and had clinical supervisors who supported HIV

prevention practices.

Perhaps the most important factor in promoting HIV prevention practices, however, seemed to be pressure from

people in the drug abuse treatment field. “When the HIV

epidemic first started, many treatment facilities were

uncertain how to react,” says Dr. D’Aunno. “As some

facilities began conducting HIV testing, counseling, and

outreach, pressure began to mount for other facilities to

do the same. This eventually created a bandwagon effect.”

NIDA helped get the bandwagon going by supporting

research programs in which scientists worked together

with practitioners to develop effective HIV/AIDS outreach techniques, according to Dr. D’Aunno. “These programs set a good example for treatment providers,” he

says. “The providers saw local researchers and other

providers working together on HIV prevention, and they

decided to follow their lead.” 

Sources

• D’Aunno, T.; Folz-Murphy, N.; and Lin, X. Changes

in methadone treatment practices: Results from a

panel study, 1988-1995. American Journal of Drug

and Alcohol Abuse 25(4):681- 699, 1999. 

• D’Aunno, T.; Vaughn, T.E.; and McElroy, P. An institutional analysis of HIV prevention efforts by the

Nation’s outpatient drug abuse treatment units.

Journal of Health and Social Behavior 40(2):175-192,

1999. 
Research Findings

40

Recovery Harder for Addicts Who Start Young

Volume 14, Number 6 (March 2000)

A NIDA-funded study has demonstrated that the relapse

rate for heroin addicts increases with time and that the

probability of long-run abstinence depends on the age 

of first drug use. Those who start daily heroin use at a

younger age are more likely to relapse than those who 

start later.

The study, conducted by Dr. Marnik G. Dekimpe of the

Catholic University Leuven in Belgium and his colleagues

in Belgium and at the University of California, Los

Angeles, examined the treatment histories of 846 patients

at methadone clinics in central and southern California.

The researchers looked at males and females, whites and

Chicanos, most of whom started using heroin between the

ages of 17 and 25. Subjects were interviewed over a 4-year

period during and after treatment to determine the probability of their relapse to heroin use.

The finding that relapse is connected to time suggests the

need for long-term periodic monitoring of a former heroin user’s abstinence, Dr. Dekimpe says. The researchers

also found drug relapse odds were significantly different

across the sociodemographic groups studied, suggesting

that prevention resources could be directed to groups at

higher risk. No significant differences in relapse probability were associated with either gender or education. 
Research Findings

41

Volume 14, Number 5 (December 1999)

High-Dose Methadone Improves Treatment Outcomes

By Patrick Zickler, NIDA NOTES Staff Writer 

Methadone has been used effectively for more than 30

years as a treatment for heroin addiction. The medication

blocks heroin’s narcotic effects without creating a drug

“high,” eliminates withdrawal symptoms, and relieves the

craving associated with addiction. Methadone is administered orally in licensed clinics and its effects typically last

24 to 36 hours. 

Although methadone has been used for decades, no 

clinical consensus has been reached about the most effective daily dose. Many clinics do not adjust dosages according to the needs of individual patients. Instead, they

administer fixed doses. One clinic might use doses of 25

milligrams (mg) per day for all patients; others may

administer daily doses of 60 mg. “Federal regulations

require that a clinic receive a special exemption in order to

provide patients with doses greater than 100 mg per day,

but no contemporary studies have examined the effectiveness of daily doses greater than 80 mg,” says Dr. Eric

Strain, a NIDA-supported researcher at The Johns

Hopkins University Medical Center in Baltimore. 

Dr. Strain and his colleagues investigated the effectiveness

of high-dose—80 to 100 mg per day—methadone treatment and found this dosage to be more effective in reducing heroin use than treatment with a moderate dose of 40

to 50 mg per day. The study involved 192 patients. Sixtyfive percent of participants were male; pregnant women

were excluded from the study group. 

During the first week of treatment all patients received

30-mg daily methadone doses. Daily doses were increased

until, by the 8th week, half the patients were receiving a

moderate dose of 40 to 50 mg per day and the other half

were receiving a high dose of 80-to-100 mg per day. These

doses were maintained through the study’s 30th week.

Dosages were then decreased by 10 percent each week

during the final 10 weeks of the program. Patients were

encouraged to enroll in long-term community-based treatment programs following completion of the 40-week

study. 

Dr. Strain and his colleagues evaluated the effectiveness of

treatment through analysis of twice-weekly observed urine

testing, weekly patient reports of heroin use, and the

length of time patients remained in treatment. “The highdose group used opiates significantly less during treatment

than did the moderate-dose group on average,” Dr. Strain

says. “Patients in the high-dose group reported using 

opiates no more than once a week. The moderate-dose

group reported using drugs two to three times per week

on average.” Among patients who completed the 30-week

active phase, 33 percent of high-dose patients remained in

treatment throughout a 10-week methadone phase-out,

compared with 20 percent of moderate-dose patients.

There were no gender-related differences in outcome for

high- or moderate-dose groups, and no difference was

reported between the high- and moderate-dose patients

for side effects such as grogginess or constipation. 

In an earlier study, the researchers found that moderatedose treatment of 50 mg per day was more effective than

low-dose treatment of 20 mg per day. “The current study

provides strong evidence that we can achieve much better

outcomes at dose rates much higher than 50 mg per day,”

Dr. Strain says. 

Dosages exceeding the currently regulated ceiling of 100

mg per day may provide the best result for some patients,

Dr. Strain says, but he notes that clinical trials would be

needed to support changing this regulation. “The most

important aspect of our research from a therapeutic and

public health perspective is that methadone treatment over

a broad range of doses results in significant clinical

improvement for opioid-addicted patients,” he says. 

Following a 1-week orientation period, patients receiving highdose (80-100 mg) methadone treatment had less self-reported

heroin use and lower rates of drug-positive urine samples than

patients on moderate-dose (40-50 mg) treatment. Urine results

are shown as 3-week averages of twice-weekly samples.
42

Sources

• Strain, E.C.; Bigelow, G.E.; Liebson, I.A.; and Stitzer,

M.L. Moderate- vs high-dose methadone in the treatment of opioid dependence: A randomized trial.

Journal of the American Medical Association

281(11):1000-1005, 1999. 

• Strain, E.C.; Stitzer, M.L.; Liebson, I.A.; and Bigelow,

G.E. Dose-response effects of methadone in the treatment of opioid dependence. Annals of Internal

Medicine 119:23-27, 1993. 
Research Findings

43

Heroin Snorters Risk Transition To Injection Drug Use and

Infectious Disease

By Robert Mathias, NIDA NOTES Staff Writer

Volume 14, Number 2 (August 1999)

Heroin users who think they can avoid the harmful consequences of drug injection by snorting or smoking the drug

may be dangerously mistaken. A NIDA-funded study

indicates that noninjecting heroin users (NIUs) are at considerable risk of becoming drug injectors, thereby incurring risks for HIV, hepatitis, and other serious diseases.

Moreover, regardless of whether they go on to inject

drugs, a significant number contract hepatitis, the study

shows. 

“Becoming a drug injector is not inevitable for heroin

snorters who have never injected drugs, but the risk of

making the transition to injection drug use is fairly substantial,” says Dr. Alan Neaigus of National Development

and Research Institutes (NDRI), Inc., in New York City.

Dr. Neaigus and his colleagues at NDRI have been examining rates of transition to injection drug use and disease

incidence among 560 NIUs recruited from March 1996

through April 1998. The study group consists of heroin

users who have never injected drugs and former heroin

injectors who had not injected drugs for at least 6 months

prior to the study. Data from followup interviews conducted with 331 study participants show that more than

15 percent transitioned to drug injection during an average period of a little more than a year. The researchers

found no significant difference in the transition rate

between NIUs who had never injected heroin and the 31

percent of the study group who were former injectors.

Previous studies have found higher rates of transition from

noninjection to injection drug use, particularly among former injectors. However, Dr. Neagius says a number of factors may now be slowing the rate at which heroin snorters

are initiating or resuming injection of the drug. First, a

dramatic increase in the purity of heroin during the 1990s

has made it possible for snorters to achieve a high that is

similar to what they can obtain from injection. Second,

greater awareness of the risk of contracting AIDS from

injecting drugs may be dissuading more users from the

practice.

The NIU study supported earlier research findings that

NIUs who socialize, use drugs, or have sex with IDUs significantly increase their risk of crossing the line from

snorting to injecting drugs. Preliminary analysis further

suggests that being in the presence of an IDU who is

injecting drugs may play an important role both in the

initiation and resumption of injection drug use, Dr.

Neaigus says. This finding suggests that the direct transfer

of information and techniques used to inject drugs may be

an important factor in the transition to injection drug use.

The level of heroin addiction is another major factor in

the transition to injection. The NIU study participants’

levels of addiction ranged from snorting heroin occasionally on weekends through using several bags a day,

“This is the era of AIDS, and everyone

knows about the risks from needles.

When you sniff, you don’t have to

worry about AIDS.” 

—Noninjecting heroin user 

interviewed in New York City

Hepatitis C Among Noninjecting Heroin Users

Drug injection is the primary mode of hepatitis C transmission. In

a New York City study, a large percentage of noninjecting heroin

users who transitioned to injection drug use contracted the disease.
44

Dr. Neaigus says. Previous research has suggested that

even with the availability of high-purity heroin, more

heavily addicted heroin snorters may turn to drug injection because it remains a more effective way to take the

drug. For example, in a study conducted between 1991

and 1993 by Dr. Samuel R. Friedman, also of NDRI, 30

percent of 755 IDUs in Brooklyn, New York, reported

they started to inject to get a better high.

NIUs and Infectious Disease

The health risks associated with noninjecting heroin use

are substantial, both for NIUs who become IDUs and for

those who don’t, the study found. All study participants

received counseling about the risks of drug injection,

hepatitis, and HIV. Nevertheless, almost 23 percent of the

NIUs who began to inject drugs contracted hepatitis C

(HCV) over the average followup period of a little over a

year. HCV leads to chronic liver infection in about 80

percent of patients, most of whom eventually develop fatal

liver diseases such as cirrhosis and liver cancer, says Dr.

Henry Francis, who directs NIDA’s Center on AIDS and

Other Medical Consequences of Drug Abuse.

Because injection drug use is the primary mode of HCV

transmission, “the rapid rate of transmission of hepatitis C

among NIUs who initiate or resume injecting was expected,” Dr. Neaigus says. “However, it is still alarming,” he

adds. What was unexpected was that some NIUs who did

not begin to inject drugs—about 4 percent—also contracted HCV during the followup period. NDRI

researchers now are attempting to determine how these

NIUs contracted the infection, Dr. Neaigus says.

NIUs who did not transition to injection drug use were

also at substantial risk of becoming infected with hepatitis

B (HBV), the study shows. About 9.5 percent contracted

HBV during the followup period. Though it receives less

attention than HCV, HBV can develop into chronic infection and serious liver disease in up to 20 percent of cases,

says NIDA’s Dr. Francis.

The considerable amount of HBV found among NIUs,

particularly among those who have never injected, reflects

substantial sexual transmission of this disease, Dr. Neaigus

says. Though the study only measured sexual activity over

a 30-day period, “we found a lot of sexual risk in this

group,” he says. For example, about 70 percent of NIUs

were sexually active during this period with two-thirds of

them engaging in unprotected sex, many with partners

who had HIV or were IDUs, says Dr. Neaigus.

To date, the study has not found any new cases of HIV

either among NIUs who began injecting drugs or among

those who did not. However, Dr. Neaigus says that the

high rates of new HBV and HCV infections found among

NIUs may serve as markers for sexual behaviors and drug

injection practices that continue to put NIUs at risk for

infection with HIV. In addition to finding extensive highrisk sexual activity among NIUs, the study found NIUs

who had recently transitioned to injection drug use commonly shared injection equipment, such as cookers, cotton, and rinse water. However, they infrequently shared

syringes and over half obtained all their syringes from

syringe exchange programs.

Noninjection drug use is two-edged in its effect on heroin

users’ risk of contracting infectious diseases, Dr. Neaigus

concludes. On the one hand, the considerable numbers of

former IDUs who are now snorting heroin instead of

injecting it have reduced their risk of AIDS and HCV

considerably. On the other hand, NIUs who have never

used heroin before have increased their risk of heroin

addiction, transition to injection drug use, and contracting HIV, HCV, and HBV.

Sources

• Neaigus, A., et al. Trends in the noninjected use of

heroin and factors associated with the transition to

injecting. In J.A. Inciardi and L.D. Harrison (eds.),

Heroin in the Age of Crack Cocaine, Thousand Oaks,

CA: Sage Publications, Inc., pp. 131-159, 1998.

• Neaigus, A.; Friedman, S.R.; Hagen, D.L.; Miller, M.;

and Des Jarlais, D.C. Transitions to injecting and

seroconversions for HIV, hepatitis B, and hepatitis C

among non-injecting heroin users. Paper presented at

the 12th World AIDS Conference, Geneva, 1998.

• Neaigus, A.; Hagen, D.L.; Friedman, S.R.; Miller, M.;

and Des Jarlais, D.C. Transitions to injecting drug use

among non-injecting heroin users. Paper presented at

the American Public Health Association annual meeting, Washington, DC, 1998. 

NIUs who socialize, use drugs, or

have sex with IDUs significantly

increase their risk of crossing the line

from snorting to injecting drugs.
Research Findings

45

Linking Medical Care With Drug Abuse Treatment Stems

Tuberculosis Among HIV-Infected Drug Users

By Robert Mathias, NIDA NOTES Staff Writer 

Volume 13, Number 3 (July 1998)

Injecting drug users with HIV/AIDS can be treated successfully for tuberculosis (TB) in methadone treatment

programs that provide comprehensive medical care,

according to NIDA-supported research. Integrating medical care and drug abuse treatment also has been effective

in preventing new cases of TB from developing among

HIV-positive patients, the research indicates. 

“A key to dealing successfully with infectious diseases,

such as TB and HIV, among drug abuse patients is the

linkage of primary care and drug abuse treatment in a

drug abuse treatment setting,” says Dr. Paul A. Coulis

of NIDA’s Center on AIDS and Other Medical Consequences of Drug Abuse. “In places where this has been

done, such as New York City, it has been effective, so we

know it works,” he says. 

TB is a chronic and infectious lung disease. People with

latent tuberculosis infection do not have symptoms, may

not develop active disease, and cannot spread TB.

However, if such individuals do not receive preventive

therapy, they may develop active TB, which is contagious. 

Research has shown that injecting drug users have high

rates of latent tuberculosis infection. NIDA-supported

studies among injecting drug users have shown that HIV

can activate this latent TB infection and increase the risk

that active TB will develop. In New York City, which was

hard hit by the linked epidemics of HIV and TB during

the mid-1980s and early 1990s, 30 percent of persons

with active TB were injecting drug users, according to the

Centers for Disease Control and Prevention (CDC). 

Rates of TB have declined both nationally and in New

York City since 1992. However, injecting drug users continue to be at high risk for HIV and tuberculosis. For

example, about one-third of the 900 methadone treatment

patients in the Montefiore Medical Center’s Substance

Abuse Treatment Program in The Bronx, New York, have

HIV, and TB rates are much higher than they are in the

general population, says Dr. Marc Gourevitch, who directs

a NIDA-funded study of TB infection in drug users

enrolled in the program. “Almost all the active TB cases

we see among drug users in our program are among those

who are HIV-positive,” Dr. Gourevitch notes. 

To respond to the complex health needs of its patients, the

Montefiore treatment program used funding from NIDA

and the Health Resources and Services Administration to

begin providing medical care on site along with methadone treatment in 1989. In addition to general and HIVrelated primary care, on-site services now include mental

health and social support services; HIV testing and counseling; and TB testing, prevention, and treatment. 

“Our model has been to build comprehensive primary

care services into the same site at which people are receiving their drug treatment to make it easier for them to get

their medical care,” Dr. Gourevitch says. This treatment

model has enabled the program to achieve excellent success in getting drug abuse treatment patients to complete

the full course of TB therapy needed to curtail the spread

of the disease, he says. 

Patients must follow demanding medication regimens to

prevent and treat TB. To complete the full course of TB

prevention, injecting drug users with latent TB infection

must take one medication, isoniazid, daily for up to a

year. Patients with active tuberculosis require an initial

hospitalization with a 4-medication regimen and then

must take 2 to 4 medications daily or several times a week

for up to a year. Failure to complete the full course of TB

treatment can spawn an even more deadly form of the disease, one that is resistant to tuberculosis medications. 

In 1989, the Montefiore treatment program implemented

a strategy called directly observed therapy (DOT) that was

designed to increase patients’ adherence to TB therapy.

With DOT, treatment personnel observe patients taking

each dose of their TB prevention and treatment medications. Now a widely accepted TB treatment practice,

DOT, along with improved management of TB cases to

ensure completion of a full course of therapy, has been

credited by the CDC as playing a major role in the overall

reduction in TB rates in the United States since 1992 (see

“The Rise and Fall of TB in the United States.”).

Methadone treatment programs offer an ideal setting to

implement DOT and ensure that injecting drug users

complete the full course of treatment because patients are

coming in daily for their methadone anyway, Dr.

Gourevitch says. “It’s a natural process to administer the
46

anti-TB medications and methadone at the same time

under direct supervision,” he says. 

Directly observed tuberculosis prevention and treatment

are voluntary at Montefiore. No incentives are offered for

participating in supervised preventive therapy, and

methadone is not withheld if drug abuse treatment

patients do not accept TB therapy. “Yet, almost everyone

opts for observed therapy because it eliminates the hassle

of having to remember to take TB medications at other

times of the day,” Dr. Gourevitch says. 

Research conducted by Dr. Gourevitch shows that a high

percentage of patients receiving directly observed prophylaxis and treatment in the context of their methadone

treatment adhere to and complete TB therapy. In one

study, more than 80 percent of 114 eligible patients had

completed or were still receiving prophylaxis or treatment

at the end of a 2-year period. Additional research by Dr.

Gourevitch indicates that completion of TB prophylaxis

was associated with a 75-percent reduction in the TB rate

in this high-risk population and that providing on-site

directly observed prophylaxis is cost-effective in terms of

preventing the costs of treating active TB. 

“What we’ve learned is that having primary care integrated

with drug abuse treatment is a very effective way to treat

and prevent various diseases among drug users,” concludes

NIDA’s Dr. Coulis. 

Sources 

• Gourevitch, M.N.; Alcabes, P.; Wasserman, W.C.; and

Arno, P. Cost-effectiveness of directly observed

chemoprophylaxis of tuberculosis among drug users at

high risk for tuberculosis. Journal of Tuberculosis and

Lung Disease, 1998. 

• Gourevitch, M.N.; Hartel, H.; Schoenbaum, E.E.;

Selwyn, P.A.; and Klein, R.S. Effectiveness of isoniazid

(INH) chemoprophylaxis in tuberculin-positive drug

users with HIV infection. Abstract presented at the

Conference on Global Lung Health and the 1997

Annual Meeting of the IUATLD, Paris, France, 1997. 

• Gourevitch, M.N.; Wasserman, W.; Panero, M.S.; and

Selwyn, P.A. Successful adherence to observed prophylaxis and treatment of tuberculosis among drug

users in a methadone program. Journal of Addictive

Diseases 15(1):93-104, 1996. 

• Herman, M., and Gourevitch, M.N. Integrating primary care and methadone maintenance treatment:

Implementation issues. Journal of Addictive Diseases

16(1):91-102, 1997. 
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